A Study to Assess the Reaction of Body for Four Different Formulations of AZD9977 (Part A) and Influence of Food and Lower Dose of a Selected Formulation (Part B) in Healthy Male Subjects

NCT ID: NCT03804645

Last Updated: 2021-04-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-05

Study Completion Date

2019-04-16

Brief Summary

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AZD9977 is an oral, selective mineralocorticoid receptor (MR) modulator. AZD9977 is a partial antagonist and partial agonist in reporter gene assays and has a different interaction pattern with the MR compared to eplerenone.

This study will assess the pharmacokinetics (PK) of four different Formulations of AZD9977 (Part A) and influence of food and lower dose of a selected formulation (Part B) in healthy male subjects.

Detailed Description

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This study will be a randomized, open-label, single-centre crossover study in healthy male subjects. The study is divided into 2 parts, Part A and Part B. The subjects will participate in both Part A and Part B.

Part A will be a 4-way cross-over study comparing the PK of AZD9977 as a reference capsule and 2 different capsule formulations and a tablet formulation under fasting conditions.

* Treatment A: Reference, AZD9977 capsule
* Treatment B: AZD9977 HDL capsule
* Treatment C: AZD9977 ODL capsule
* Treatment D: AZD9977 tablet In Part B, based on the interim results in Part A, 1 of the formulations will be selected and evaluated at the 300 mg dose level under fed conditions. The same formulation will also be evaluated under fasting conditions at a lower dose level (50 mg). The first dose tested in Part B will be the 50 mg (fasted) dose, followed by the 300 mg (fed) dose.

In Part A, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1) with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 4). Subjects will return to the unit for Part B at least 48 hours (and up to 5 weeks) after completion of Part A.

In Part B, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1) with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 2).

Subjects will return to the unit for a final study visit 5-7 days post-last-dose for a Follow up Visit.

Each subject will be involved in the study for approximately 12 weeks (including approximately 4 to 5 weeks for the interim analysis).

Twelve subjects will initially be randomized to ensure at least 8 and 6 evaluable subjects at the end of the last treatment period for Part A and Part B respectively.

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

open-label, randomized, four-way crossover single oral dose
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

This is an open-label study.

Study Groups

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Cohort 1

In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment B

Intervention Type DRUG

Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment C

Intervention Type DRUG

Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.

Treatment D

Intervention Type DRUG

Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Cohort 2

In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment B

Intervention Type DRUG

Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment C

Intervention Type DRUG

Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.

Treatment D

Intervention Type DRUG

Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Cohort 3

In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment B

Intervention Type DRUG

Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment C

Intervention Type DRUG

Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.

Treatment D

Intervention Type DRUG

Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Cohort 4

In Part A, each subject will receive AZD9977 as a single dose on 4 different occasions under fasting conditions, separated by at least 48 hours.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment B

Intervention Type DRUG

Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment C

Intervention Type DRUG

Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.

Treatment D

Intervention Type DRUG

Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Cohort 5

In Part B, each subject will receive one formulation from Part A chosen for further development, dose under fed conditions, followed by dose under fasted condition.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment B

Intervention Type DRUG

Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Treatment C

Intervention Type DRUG

Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.

Treatment D

Intervention Type DRUG

Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Interventions

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Treatment A

Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Intervention Type DRUG

Treatment B

Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Intervention Type DRUG

Treatment C

Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.

Intervention Type DRUG

Treatment D

Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.

Intervention Type DRUG

Other Intervention Names

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AZD9977 capsule, reference AZD9977 HDL capsule AZD9977 ODL capsule AZD9977 tablet

Eligibility Criteria

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Inclusion Criteria

1. Provision of signed and dated, written informed consent prior to any study specific procedures.
2. Agree to use the methods of contraception.
3. Healthy male subjects aged 18 to 50 years, inclusive, with suitable veins for cannulation or repeated venipuncture at screening.
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 at screening.
5. Subject judged at screening likely to complete and agree to eat a specified high fat standardized Food and Drug Administration (FDA) breakfast.

Exclusion Criteria

1. History of any clinically significant disease or disorder which, in the opinion of the principal investigator (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, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
4. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI, including:

4.1. Serum potassium \> 5.0 mmol/L.
5. Any clinically significant abnormal findings in vital signs, as judged by the PI, including:

5.1. Systolic BP \< 90 mmHg or \> 140 mmHg. 5.2. Diastolic BP \< 50 mmHg or \> 90 mmHg. 5.3. Pulse rate \< 45 or \> 90 beats per minute.
6. Any clinically significant abnormalities on 12-lead echocardiogram (ECG), as judged by the PI.
7. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
8. Known or suspected history of drug abuse in the 12 months prior to screening, as judged by the PI.
9. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of AZD9977 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: subjects consented and screened, but not randomized in this study or a previous Phase 1 study, are not excluded.
10. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
11. 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 AZD9977.
12. Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening.
13. Positive screen for drugs of abuse, alcohol or cotinine at screening or on admission to the study center.
14. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of AZD9977.
15. 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 the first administration of AZD9977 or longer if the medication has a long half life.
16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol in the 12 months prior to screening as judged by the PI.
17. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
18. Subjects who have previously received AZD9977.
19. Judgment by the PI that the subject 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.
20. Vulnerable subjects, 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

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pablo Forte Soto, MD, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Dr.

Locations

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Research Site

Harrow, , United Kingdom

Site Status

Countries

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United Kingdom

Related Links

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https://astrazenecagrouptrials.pharmacm.com/ST/Submission/View?id=25801

Study Information posted to AstraZeneca Cinical Trials Webiste

Other Identifiers

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D6401C00006

Identifier Type: -

Identifier Source: org_study_id

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