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

Healthy Volunteers Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05457270
• Other study ID #: D6580C00016
• Status: Completed
• Phase: Phase 1
• Start date: August 11, 2022
• Est. completion date: October 17, 2022

Study information

• Verified date: October 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 17, 2022
• Est. primary completion date: October 17, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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.

Locations

Country	Name	City	State
United States	Research Site	Brooklyn	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (?z)	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
Primary	Half-life associated with terminal slope (?z) of a semi-logarithmic concentration-time curve (t1/2?z)	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
Primary	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
Primary	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
Primary	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	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)