A Study to Assess the Relative Bioavailability and Safety of Different Formulations of AZD4831 in Fasted State in Healthy Volunteers.
Study Details
Study Description
Brief Summary
A study to assess the relative bioavailability and safety of different formulations of AZD4831 in fasted state in healthy volunteers.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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:
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A Screening Period of maximum 28 days.
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Period 1: single oral dose AZD4831 Formulation A or B on Day 1.
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Period 2: single oral dose AZD4831 Formulation A or B on Day 1.
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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
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Treatment 1 (Reference), AZD4831 Formulation A, oral dosage form), fasted.
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Treatment 2 (Test), AZD4831 Formulation B, oral dosage from), fasted.
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision of signed and dated, written informed consent prior to any study-specific procedures.
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Male participants must adhere to the contraception methods.
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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:
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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.
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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:
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Any clinically significant abnormalities on 12-lead Electrocardiogram (ECG) at the Screening Visit, as judged by the Investigator.
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Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
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History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
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Known or suspected Gilbert's syndrome.
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History or ongoing allergy/hypersensitivity to drugs (including, but not limited to rash, angioedema, acute urticaria).
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Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks before the first administration of AZD4831.
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Participants who previously received AZD4831.
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Any of the following signs or confirmation of COVID-19 infection:
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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.
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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.
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Participant has been hospitalized with COVID-19 infection within the last 3 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Brooklyn | Maryland | United States | 21225 |
Sponsors and Collaborators
- AstraZeneca
- Parexel
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D6580C00016