A Study to Assess the Relative Bioavailability and Safety of Different Formulations of AZD4831 in Fasted State in Healthy Volunteers.

A Randomized, Single-dose, Open-label, Single-center, Crossover Study to Assess the Relative Bioavailability and Safety of Different Formulations of AZD4831 in Fasted State in Healthy Volunteers.

A study to assess the relative bioavailability and safety of different formulations of AZD4831 in fasted state in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: AZD4831

Detailed Description

This study will be a randomized, open-label, 2-period, 2-treatment, single-dose, single-center, crossover study conducted at a single Clinical Unit. A total of 30 healthy male and female participants will be randomized to ensure that at least 26 participants are evaluable .

The study will comprise of:

• A Screening Period of maximum 28 days.
• Period 1: single oral dose AZD4831 Formulation A or B on Day 1.
• Period 2: single oral dose AZD4831 Formulation A or B on Day 1.
• A final Follow-up Visit after the last administration of Investigational medicinal product (IMP) (14 days [+ 3 days] post final dose).

There will be a minimum washout period of at least 14 days from the first dose of AZD4831.

Participants will receive single doses of AZD4831 (2 different formulations) on 2 occasions under fasted conditions.

Participants will be given the following treatments and randomly assigned to the treatment sequence(s): AB, BA

• Treatment 1 (Reference), AZD4831 Formulation A, oral dosage form), fasted.
• Treatment 2 (Test), AZD4831 Formulation B, oral dosage from), fasted.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study-specific procedures.
• Male participants must adhere to the contraception methods.

• Females must have a negative pregnancy test at screening and on admission to the Clinical Unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:

  1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and Follicle-stimulating hormone (FSH) levels in the postmenopausal range.
  2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Have a Body mass index (BMI) between 18.5 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg inclusive at Screening.

Exclusion Criteria:

• Any clinically significant abnormalities on 12-lead Electrocardiogram (ECG) at the Screening Visit, as judged by the Investigator.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Known or suspected Gilbert's syndrome.
• History or ongoing allergy/hypersensitivity to drugs (including, but not limited to rash, angioedema, acute urticaria).
• Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks before the first administration of AZD4831.
• Participants who previously received AZD4831.

• Any of the following signs or confirmation of COVID-19 infection:

  1. Participant has a positive SARS-CoV-2 reverse transcription-PCR test result within 2 weeks before the Screening Visit or between the Screening Visit and Randomization.
  2. Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnea, sore throat, fatigue) 2 weeks before the Screening Visit or between the Screening Visit and Randomization.
  3. Participant has been hospitalized with COVID-19 infection within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1 (Formulation A + Formulation B); Participants will receive a single oral dose of Treatment 1: Formulation A followed by a washout period of at least 14 days from first dose of AZD4831. After the washout period, participants will receive a single oral dose of Treatment 2: AZD4831 Formulation B.	Drug: AZD4831; Participants will receive a single oral dose of AZD4831 Formulation A Or a single oral dose of AZD4831 Formulation B on Day 1 Period 1. Depending on what Formulation was received on Day 1 Period 1, participants will receive either a single oral dose of AZD4831 Formulation A Or a single oral dose of AZD4831 Formulation B on Day 1 of Period 2. Each period lasts for 8 days.
Experimental: Sequence 2 (Formulation B + Formulation A); Participants will receive a single oral dose of Treatment 2: Formulation B followed by a washout period of at least 14 days from first dose of AZD4831. After the washout period, participants will receive a single oral dose of Treatment 1 Formulation A.	Drug: AZD4831; Participants will receive a single oral dose of AZD4831 Formulation A Or a single oral dose of AZD4831 Formulation B on Day 1 Period 1. Depending on what Formulation was received on Day 1 Period 1, participants will receive either a single oral dose of AZD4831 Formulation A Or a single oral dose of AZD4831 Formulation B on Day 1 of Period 2. Each period lasts for 8 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative bioavailability (Frel)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Maximum observed plasma (peak) drug concentration (Cmax)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Area under plasma concentration-time curve from zero to infinity (AUCinf)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Time of last observed (quantifiable) concentration (tlast)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Last observed (quantifiable) concentration (Clast)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14
Time to reach peak or maximum observed concentration or response following drug administration (tmax)	The relative bioavailability of a new AZD4831 formulation compared to the formulation used in an ongoing Phase 2b study and in a couple Phase 1 studies in healthy volunteers will be evaluated.	Day 1, Day 2 to Day 8 and Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs)	The safety and tolerability of single doses of AZD4831 in healthy volunteers will be assessed.	From Screening until Follow up visit (At 14 days post final dose)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Actual): October 17, 2022
• Study Completion (Actual): October 17, 2022

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Relative Bioavailability; Heart failure with preserved ejection fraction; AZD4831
• Other Study ID Numbers: D6580C00016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing 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
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No