Clinical trial NCT05457270: A Study to Assess the Relative Bioavailability and Safety of Different Formulations of AZD4831 in Fasted State in Healthy Volunteers.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Relative Bioavailability
AZD4831
Heart failure with preserved ejection fraction
Cardiovascular disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-07-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Relative bioavailability (Frel)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Maximum observed plasma (peak) drug concentration (Cmax)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Area under plasma concentration-time curve from zero to infinity (AUCinf)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Time of last observed (quantifiable) concentration (tlast)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Last observed (quantifiable) concentration (Clast)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
measure: Time to reach peak or maximum observed concentration or response following drug administration (tmax)
timeFrame: Day 1, Day 2 to Day 8 and Day 14
Secondary outcomes:
measure: Number of participants with Adverse Events (AEs)
timeFrame: From Screening until Follow up visit (At 14 days post final dose)
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: