A Study to Assess the Effect of AZD0780 on the Pharmacokinetics of Rosuvastatin.

Study Overview
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Brief Summary
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The purpose of the study is to assess the effect of AZD0780 on the pharmacokinetics of rosuvastatin, and to assess the safety and tolerability of AZD0780 single dose, in healthy participants administered alone and in combination with rosuvastatin.

Detailed Description
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Eligible participants will be randomized, in a 1:1 ratio into 2 of the treatment arms. Each participant will receive 2 treatments in total throughout the study. The following treatments will be given in randomized order in fasting state: Treatment A: single dose of rosuvastatin tablet alone Treatment B: single dose of rosuvastatin tablet + AZD0780 tablet The study will comprise: A Screening Period of maximum 28 days. Two Treatment Periods up to 3 days A follow-up period of 10 to 12 days after the last administration of the study drug. Following an overnight fast (minimum 10 hours) participants will receive either of the two treatments and will remain resident in the Clinical Unit until up to 48 hours after dosing of the study drug (up to Day 3). The total duration of the study will be up to 9 weeks.

Official Title
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An Open-label, 2-Period, 2-Sequence Cross-over Study to Assess the Effect of AZD0780 on the Pharmacokinetics of Rosuvastatin in Healthy Participants

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: AZD0780
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study specific procedures. Healthy male and female participants (of non-childbearing potential) aged 18 to 60 years, inclusive, with suitable veins for cannulation or repeated venipuncture. Females must have a negative pregnancy test at screening and must not be lactating Participants with BMI between 18 and 30 kg/m^2, inclusive, and weighing between 50 kg and 100 kg, inclusive Exclusion Criteria: History or presence of gastrointestinal, hepatic or renal disease, or any other clinically significant disease or disorder Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first vaccination within 30 days prior to randomization and second vaccination within 10 days of screening Confirmed Coronavirus disease 2019 (COVID-19) infection at admission, by Polymerase chain reaction (PCR) test Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening History or presence of severe allergy/hypersensitivity Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening Positive screen for drugs of abuse, alcohol, or cotinine at screening Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of the study drug Any clinically significant abnormalities in clinical chemistry, hematology, coagulation, urinalysis results, ECG or vital signs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be randomized, in a 1:1 ratio into each of the treatment arms prior to the study commencing. Each participant will receive 2 treatments in total throughout the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence A-B<br>Participants will receive treatments in the following sequence, a single dose of rosuvastatin tablet alone (Treatment A) in period 1, and then a single dose of rosuvastatin tablet + Dose X AZD0780 tablet (Treatment B) in period 2. | Drug: AZD0780<br>* AZD0780 will be administered orally as a single dose after an overnight fast of at least 10 hours with approximately 240 mL of water.<br>Drug: Rosuvastatin<br>* Rosuvastatin will be administered orally as a single dose after an overnight fast of at least 10 hours with approximately 240 mL of water.<br>|
| Experimental: Treatment sequence B-A<br>Participants will receive 1 treatment during each study period in the following sequence: a single dose of rosuvastatin tablet + AZD0780 tablet (Treatment B) in period 1 and then a single dose of rosuvastatin tablet alone (Treatment A) in period 2. | Drug: AZD0780<br>* AZD0780 will be administered orally as a single dose after an overnight fast of at least 10 hours with approximately 240 mL of water.<br>Drug: Rosuvastatin<br>* Rosuvastatin will be administered orally as a single dose after an overnight fast of at least 10 hours with approximately 240 mL of water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of Rosuvastatin | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast) of Rosuvastatin | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Maximum observed plasma concentration (Cmax) of Rosuvastatin | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Terminal elimination half-life (t½λz) of Rosuvastatin | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Time to reach maximum observed concentration (tmax) of Rosuvastatin | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Apparent total body clearance (CL/F) of Rosuvastatin | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Rosuvastatin | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of AZD0780 | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD0780 | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Maximum observed plasma concentration (Cmax) of AZD0780 | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Time to reach maximum observed concentration (tmax) of AZD0780 | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Terminal elimination half-life (t½λz) of AZD0780 | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Apparent total body clearance (CL/F) of AZD0780 | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 
| Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD0780 | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events | The safety and tolerability of AZD0780 in combination with rosuvastatin in healthy participants will be assessed. | From Screening (≤ 28 days to Day -2) until Follow-up Visit (10 to 12 days post-final dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolemia, elevated Low-density lipoprotein-cholesterol (LDL-C) levels, Drug-drug interaction, Healthy Participants