Healthy Volunteers
Conditions
Keywords
Relative Bioavailability, AZD4831, Heart failure with preserved ejection fraction, Cardiovascular disease
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.
Interventions
DRUGAZD4831
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.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach peak or maximum observed concentration or response following drug administration (tmax) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Relative bioavailability (Frel) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Maximum observed plasma (peak) drug concentration (Cmax) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Area under plasma concentration-time curve from zero to infinity (AUCinf) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Time of last observed (quantifiable) concentration (tlast) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
| Last observed (quantifiable) concentration (Clast) | Day 1, Day 2 to Day 8 and Day 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events (AEs) | From Screening until Follow up visit (At 14 days post final dose) | The safety and tolerability of single doses of AZD4831 in healthy volunteers will be assessed. |
Countries
United States
Outcome results
None listed