Study to Assess the Effect of AZD4831 on the Pharmacokinetics (Drug Behavior in the Body) of Midazolam
Study Details
Study Description
Brief Summary
The study is an open-label, fixed-sequence, cross-over study conducted at a single Clinical Unit to assess the pharmacokinetics (PK) of midazolam in healthy male and female (non-childbearing potential) subjects when administered alone and in combination with AZD4831 after multiple doses (once daily) of AZD4831 for 10 consecutive days.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study will consist of 2 treatment periods and will comprise:
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A Screening period of maximum 28 days;
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Treatment Period 1 and Treatment Period 2:
Treatment Period 1: Midazolam only (Day 1). Treatment Period 2: AZD4831 only (Days 2 to 10, once daily dosing) and AZD4831 plus midazolam (Day 11).
- A final Follow-up Visit after the last administration of investigational medicinal product (IMP) (Day 20 [± 1 day]).
Each subject will be involved in the study for approximately 7 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm Subjects will receive midazolam on Day 1 and AZD4831 once daily from Days 2 to 10, and AZD4831 plus midazolam on Day 11. |
Drug: AZD4831
Subjects will receive oral doses once daily from Days 2-11.
Drug: Midazolam
Subjects will receive oral single doses on Day 1 and Day 11.
|
Outcome Measures
Primary Outcome Measures
- Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam [Days 1, 2, 11, and 12]
Effect of AZD4831 on AUCinf of Midazolam will be assessed.
- Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Midazolam [Days 1, 2, 11, and 12]
Effect of AZD4831 on AUClast of Midazolam will be assessed.
- Maximum observed plasma (peak) drug concentration (Cmax) of Midazolam [Days 1, 2, 11, and 12]
Effect of AZD4831 on Cmax of Midazolam will be assessed.
Secondary Outcome Measures
- Time to reach peak or maximum observed concentration or response following drug administration (tmax) of Midazolam and AZD4831 [Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12]
tmax of Midazolam and AZD4831 will be assessed.
- Half life associated with terminal slope (λz) of a semi logarithmic concentration timecurve (t½λz) of Midazolam and AZD4831 [Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12]
t½λz of Midazolam and AZD4831 will be assessed.
- Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Midazolam and AZD4831 [Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12]
CL/F of Midazolam and AZD4831 will be assessed.
- Apparent volume of distribution based on terminal phase (Vz/F) of Midazolam [Days 1, 2, 11, and 12]
Vz/F of Midazolam will be assessed.
- Area under the plasma concentration-curve across the dosing interval (AUCtau) of AZD4831 [Days 2-12]
AUCtau of AZD4831 will be assessed.
- Cmax of AZD4831 [Days 2-12]
Cmax of AZD4831 will be assessed.
- Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831 [Days 3-10]
Pre-dose plasma concentration of AZD4831 will be assessed.
- Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831 [Day 11]
Plasma concentration of AZD4831 will be assessed.
- Number of patients with adverse events (AE) and serious AEs (SAE) [From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20)]
Safety and tolerability of AZD4831 alone and in combination with midazolam will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy male and/or female subjects 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, confirmed at Screening.
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Have a body mass index between 18.5 and 30 kg/m^2 (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.
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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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A positive Corona Virus Disease 2019 test at Screening or admission to the Clinical Unit on Day -1.
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Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results.
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Any clinically significant abnormal findings in vital signs.
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clinically significant abnormalities on 12-lead electrocardiogram.
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Any positive result at the Screening Visit for Hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody.
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Known or suspected history of drug abuse in the last 2 years.
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Current smokers or those who have smoked or used nicotine products within the 3 months prior to the Screening Visit.
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Known or suspected history of alcohol or drug abuse.
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Use of any prescribed or non-prescribed medication.
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Subjects with acute pulmonary insufficiency, marked neuromuscular respiratory weakness, obsessional states, phobic states, sleep apnoea syndrome, or unstable myasthenia gravis.
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History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigatoror history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831 or midazolam.
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History or ongoing allergy/hypersensitivity to drugs(including but not limited to rash, angioedema, acute urticaria).
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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
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D6580C00012