Study to Assess the Bioavailability of Different Formulations of AZD9977 and Dapagliflozin and Influence of Food in Selected Formulations in Healthy Volunteers

NCT ID: NCT04798222

Last Updated: 2021-09-09

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

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-29

Study Completion Date

2021-09-03

Brief Summary

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The primary purpose of the study is to evaluate relative bioavailability of AZD9977 and dapagliflozin and compare the plasma concentration time profiles after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.

Detailed Description

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The study will be conducted at 2 study centers in Germany.

Eligible participants will be randomized to one of the 8 treatment sequences (4 unique sequences to Group 1 and 4 unique sequences to Group 2). In Group 1, participants will receive 5 single dose treatments, while in Group 2 participants will receive 4 single dose treatments.

Below treatments A, B, C, D and E will be given to participants in Group 1 and treatments A, F, G and H will be given to participants in Group 2 in randomized order:

1. Treatment A: AZD9977 Dose A + 10 mg dapagliflozin tablet, fasted
2. Treatment B: AZD9977 Dose A + 10 mg dapagliflozin capsule 1, fasted
3. Treatment C: AZD9977 Dose A + 10 mg dapagliflozin capsule 1, fed
4. Treatment D: AZD9977 Dose A + 10 mg dapagliflozin capsule 2, fasted
5. Treatment E: AZD9977 Dose A + 10 mg dapagliflozin capsule 2, fed
6. Treatment F: AZD9977 Dose A + 10 mg dapagliflozin capsule 3, fasted
7. Treatment G: AZD9977 Dose A + 10 mg dapagliflozin capsule 4, fasted
8. Treatment H: 10 mg dapagliflozin capsule, fasted

The study will comprise of the following:

* A screening period of maximum 21 days.
* Four or five treatment periods during which participants will be resident at the study center from the day before dosing until at least 72 hours after the final dose.
* A final visit within 5 to 7 days after administration of the last treatment.

Each participant will receive single dose treatments under fasted or fed conditions, separated by at least 4 days washout.

Each participant will be involved in the study for approximately 6 to 7 weeks.

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Group 1: Treatment Sequence ABECD

Participants will receive a single oral dose of Treatments A, B, E, C, and D in Treatment periods 1 to 5 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment B

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fasted condition.

Treatment C

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fed condition

Treatment D

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fasted condition.

Treatment E

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fed condition.

Group 1: Treatment Sequence BACED

Participants will receive a single oral dose of Treatments B, A, C, E, and D in Treatment periods 1 to 5 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment B

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fasted condition.

Treatment C

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fed condition

Treatment D

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fasted condition.

Treatment E

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fed condition.

Group 1: Treatment Sequence CDBEA

Participants will receive a single oral dose of Treatments C, D, B, E, and A in Treatment periods 1 to 5 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment B

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fasted condition.

Treatment C

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fed condition

Treatment D

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fasted condition.

Treatment E

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fed condition.

Group 1: Treatment Sequence EADBC

Participants will receive a single oral dose of Treatments E, A, D, B, and C in Treatment periods 1 to 5 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment B

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fasted condition.

Treatment C

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fed condition

Treatment D

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fasted condition.

Treatment E

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fed condition.

Group 2: Treatment Sequence AFHG

Participants will receive a single oral dose of Treatments A, F, H, and G in Treatment periods 1 to 4 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment F

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 3 in fasted condition.

Treatment G

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 4 in fasted condition.

Treatment H

Intervention Type DRUG

Participants will receive oral dose of dapagliflozin capsule in fasted condition.

Group 2: Treatment Sequence FGAH

Participants will receive a single oral dose of Treatments F, G, A, and H in Treatment periods 1 to 4 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment F

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 3 in fasted condition.

Treatment G

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 4 in fasted condition.

Treatment H

Intervention Type DRUG

Participants will receive oral dose of dapagliflozin capsule in fasted condition.

Group 2: Treatment Sequence GHFA

Participants will receive a single oral dose of Treatments G, H, F, and A in Treatment periods 1 to 4 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment F

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 3 in fasted condition.

Treatment G

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 4 in fasted condition.

Treatment H

Intervention Type DRUG

Participants will receive oral dose of dapagliflozin capsule in fasted condition.

Group 2: Treatment Sequence HAGF

Participants will receive a single oral dose of Treatments H, A, G, and F in Treatment periods 1 to 4 on Day 1 of the study.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Treatment F

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 3 in fasted condition.

Treatment G

Intervention Type DRUG

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 4 in fasted condition.

Treatment H

Intervention Type DRUG

Participants will receive oral dose of dapagliflozin capsule in fasted condition.

Interventions

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Treatment A

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin tablet in fasted condition.

Intervention Type DRUG

Treatment B

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fasted condition.

Intervention Type DRUG

Treatment C

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 1 in fed condition

Intervention Type DRUG

Treatment D

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fasted condition.

Intervention Type DRUG

Treatment E

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 2 in fed condition.

Intervention Type DRUG

Treatment F

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 3 in fasted condition.

Intervention Type DRUG

Treatment G

Participants will receive oral AZD9977 Dose A capsule and 10 mg dapagliflozin capsule 4 in fasted condition.

Intervention Type DRUG

Treatment H

Participants will receive oral dose of dapagliflozin capsule in fasted condition.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Healthy participants of non-childbearing potential with suitable veins for cannulation or repeated venipuncture at screening
* Females must have a negative pregnancy test at the screening Visit and a negative urine pregnancy test at admission to the study center, must not be lactating and must be of non childbearing potential
* Have a body mass index between 18 and 29.9 kg/m\^2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive, at screening

Exclusion Criteria

* History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the subject'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 administration of investigational medicinal product (IMP).
* Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at screening, as judged by the Investigator
* Any clinically significant abnormal findings in vital signs, and 12-lead electrocardiogram as judged by the Investigator
* Any positive result on screening for serum hepatitis B surface antigen or anti-hemoglobin antibody, hepatitis C antibody, and human immunodeficiency virus antibody
* Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months (or 5 half lives, whichever is longer) of the first administration of IMP in this study
* 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 or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977 or dapagliflozin
* Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening
* Participant has a positive test result for Severe acute respiratory syndrome coronavirus 2 reverse transcriptase polymerase chain reaction at admission
* Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP
* Use of any prescribed or non prescribed medication including antacids, analgesics, hormone replacement therapy, herbal remedies, megadose vitamins and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life
* Participants who have previously received AZD9977 or dapagliflozin
* Judgment by the Investigators that the participant should not participate in the study if they have any ongoing or recent minor medical complaints
* Participants who cannot communicate reliably with the Investigator and/or is not able to read, speak and understand the German language
* Participant has clinical signs and symptoms consistent with corona virus disease 2019 (COVID-19), or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on first admission
* History of severe COVID-19 infection (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated) as judged by the Investigator
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ozan Dursun

Role: PRINCIPAL_INVESTIGATOR

Parexel Early Phase Clinical Unit Berlin Campus DRK Kliniken Berlin Westend, Haus 31 Spandauer Damm 130 14050 Berlin Germany

Alen Jambrecina

Role: PRINCIPAL_INVESTIGATOR

CTC North GmbH & Co. KG Martinistrasse 64 20251 Hamburg Germany

Locations

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Research Site

Berlin, , Germany

Site Status

Countries

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Germany

Other Identifiers

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2021-000483-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D6402C00003

Identifier Type: -

Identifier Source: org_study_id

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