A Study to Assess the Pharmacokinetics of AZD4831 When Administered Alone and in Combination With Itraconazole
Study Details
Study Description
Brief Summary
A study to demonstrate pharmacokinetics of AZD4831 when administered alone and in combination with Itraconazole.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This will be a an open-label, 3-period fixed sequence study to be conducted at a single study centre.
The treatment starts with AZD4831 (Treatment Period 1), followed by Itraconazole administration for 3 days (Treatment Period 2) and finally a combination of AZD4831+Itraconazole administration (Treatment Period 3).
The study will comprise of:
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A Screening Period of approximately 28 days.
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Three Treatment Periods:
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Treatment Period 1 (Day -1 through pre-dose Day 8): Single oral dose of AZD4831 only on Day 1,
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Treatment Period 2 (Day 8 through pre-dose Day 11): Oral dose of Itraconazole only on Days 8 through 10,
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Treatment Period 3 (Day 11 through Day 18, after the last PK sample is collected): AZD4831 and Itraconazole on Day 11 and oral dosing of Itraconazole only on Days 12 through 17.
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A final Follow-up Visit after the last PK sample (Day 25 to Day 32).
Each subject will be involved in the study for approximately 9 weeks (including the 28 day Screening Period).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm Subjects will receive AZD4831 on Day 1; Itraconazole only on Days 8 through 10 , and AZD4831 and Itraconazole on Day 11 oral dosing of Itraconazole only on Days 12 through 17. |
Drug: AZD4831
Subjects will receive single oral dose only on Day 1 and Day 11.
Drug: Itraconazole
Subjects will receive Itraconazole orally on Days 8 followed by dosing from Day 9 to Day 17.
|
Outcome Measures
Primary Outcome Measures
- Maximum observed plasma (peak) drug concentration (Cmax) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Area under plasma concentration time curve from zero to infinity (AUCinf) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Time to reach peak or maximum observed concentration or response following drug administration (tmax) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase (Vz/F) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Terminal elimination rate constant (λz) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
- Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRTinf) for AZD4831 [Period 1: Study days 1 to 6, 8; Period 3: Study days 11 to 16, 18]
To assess the effect of Itraconazole on AZD4831 only.
Secondary Outcome Measures
- Number of subjects with adverse events (AE) [From Screening (Day -28 to Day -2) to Follow-up visit (Between Day 25 and Day 32)]
To assess safety and tolerability of AZD4831 alone and in combination with Itraconazole.
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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Healthy male and female (non-childbearing potential) subjects aged 18 to 55 years (inclusive) at the time of signing informed consent, with suitable veins for cannulation or repeated venepuncture.
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Males must be willing to use appropriate contraception methods.
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Females must not be lactating and must be of non-childbearing potential.
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Have a .BMI between 18.5 and 30.0 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive) at Screening.
Exclusion Criteria:
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History of any clinically significant disease or disorder, including hyperthyroidism, uncontrolled hypothyroidism or any clinically significant thyroid disease.
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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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Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational medicinal product (IMP).
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A positive COVID-19 test at the Screening Visit or admission to the Clinical Unit.
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Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis, vital signs, and 12-lead ECG.
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Any positive result at the Screening Visit for serum Hepatitis B surface antigen (HBsAg), HCV, and Human immunodeficiency virus (HIV) antibody.
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Known or suspected Gilbert's syndrome.
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Known or suspected history of drug abuse in the last 2 years, as judged by the Investigator.
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Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study or final follow up visit within 1 month of first administration of IMP in this study.
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Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to the Screening Visit.
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History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831 or itraconazole.
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Current smokers or those who have smoked or used nicotine products (including e cigarettes).
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Excessive intake of caffeine-containing drinks or foods.
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Known or suspected history of alcohol or excessive intake of alcohol.
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Positive screen for drugs of abuse or cotinine at screening.
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Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
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Use of any prescribed or non prescribed medication including COVID-19 vaccines, antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life.
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Subjects who have previously received AZD4831.
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Subjects who are lactose intolerant or have other specific dietary restrictions that cannot be accommodated by the Clinical Unit.
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Subjects who, in the opinion of the Investigator, have any clinically significant skin condition.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Harrow | United Kingdom | HA1 3UJ |
Sponsors and Collaborators
- AstraZeneca
- Parexel
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D6580C00013
- 2021-005727-21