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

NCT04798222 | Completed Phase 1

• 2 other identifiers: D6402C000032021-000483-30
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure

Keywords

Bioavailability; Oral selective mineralocorticoid receptor modulator; Pharmacokinetics; Dapagliflozin; AZD9977

Outcome Measures

Primary Outcomes (4)

• Area under plasma concentration time curve from zero to infinity (AUCinf)

  Evaluation of AUCinf of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

• Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast)

  Evaluation of AUClast of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

• Maximum observed plasma (peak) drug concentration (Cmax)

  Evaluation of Cmax of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

• Drug concentration in plasma at 24 hours post-dose (C24)

  Evaluation of C24 of AZD9977 and dapagliflozin, after dosing with different capsule formulations containing both AZD9977 and dapagliflozin or solely dapagliflozin, the AZD9977 capsule, and dapagliflozin tablet under fasted conditions.

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

Secondary Outcomes (13)

• AUCinf of AZD9977 and dapagliflozin

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

• AUClast of AZD9977 and dapagliflozin

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

• Cmax of AZD9977 and dapagliflozin

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

• C24 of AZD9977 and dapagliflozin

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

• AUCinf of AZD9977

  Day 1 until Day 4 of each Treatment Period (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

Study Arms (8)

Group 1: Treatment Sequence ABECD

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D; Drug: Treatment E

Group 1: Treatment Sequence BACED

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D; Drug: Treatment E

Group 1: Treatment Sequence CDBEA

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D; Drug: Treatment E

Group 1: Treatment Sequence EADBC

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C; Drug: Treatment D; Drug: Treatment E

Group 2: Treatment Sequence AFHG

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment F; Drug: Treatment G; Drug: Treatment H

Group 2: Treatment Sequence FGAH

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment F; Drug: Treatment G; Drug: Treatment H

Group 2: Treatment Sequence GHFA

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment F; Drug: Treatment G; Drug: Treatment H

Group 2: Treatment Sequence HAGF

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment F; Drug: Treatment G; Drug: Treatment H

Interventions

Treatment A DRUG

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

Group 1: Treatment Sequence ABECD; Group 1: Treatment Sequence BACED; Group 1: Treatment Sequence CDBEA; Group 1: Treatment Sequence EADBC; Group 2: Treatment Sequence AFHG; Group 2: Treatment Sequence FGAH; Group 2: Treatment Sequence GHFA; Group 2: Treatment Sequence HAGF

Treatment B DRUG

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

Group 1: Treatment Sequence ABECD; Group 1: Treatment Sequence BACED; Group 1: Treatment Sequence CDBEA; Group 1: Treatment Sequence EADBC

Treatment C DRUG

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

Group 1: Treatment Sequence ABECD; Group 1: Treatment Sequence BACED; Group 1: Treatment Sequence CDBEA; Group 1: Treatment Sequence EADBC

Treatment D DRUG

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

Group 1: Treatment Sequence ABECD; Group 1: Treatment Sequence BACED; Group 1: Treatment Sequence CDBEA; Group 1: Treatment Sequence EADBC

Treatment E DRUG

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

Group 1: Treatment Sequence ABECD; Group 1: Treatment Sequence BACED; Group 1: Treatment Sequence CDBEA; Group 1: Treatment Sequence EADBC

Treatment F DRUG

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

Group 2: Treatment Sequence AFHG; Group 2: Treatment Sequence FGAH; Group 2: Treatment Sequence GHFA; Group 2: Treatment Sequence HAGF

Treatment G DRUG

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

Group 2: Treatment Sequence AFHG; Group 2: Treatment Sequence FGAH; Group 2: Treatment Sequence GHFA; Group 2: Treatment Sequence HAGF

Treatment H DRUG

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

Group 2: Treatment Sequence AFHG; Group 2: Treatment Sequence FGAH; Group 2: Treatment Sequence GHFA; Group 2: Treatment Sequence HAGF

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Ozan Dursun

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

  PRINCIPAL INVESTIGATOR

• Alen Jambrecina

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

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 15, 2021
• Study Start: June 29, 2021
• Primary Completion: September 3, 2021
• Study Completion: September 3, 2021
• Last Updated: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

DE (1)