Dyslipidemia
Conditions
Keywords
Hypercholesterolemia, elevated Low-density lipoprotein-cholesterol (LDL-C) levels, Drug-drug interaction, Healthy Participants
Brief summary
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
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: 1. A Screening Period of maximum 28 days. 2. Two Treatment Periods up to 3 days 3. 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.
Interventions
DRUGAZD0780
AZD0780 will be administered orally as a single dose after an overnight fast of at least 10 hours with approximately 240 mL of water.
DRUGRosuvastatin
Rosuvastatin will be administered orally as a single dose after an overnight fast of at least 10 hours with approximately 240 mL of water.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD0780 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of Rosuvastatin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast) of Rosuvastatin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Maximum observed plasma concentration (Cmax) of Rosuvastatin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Terminal elimination half-life (t½λz) of Rosuvastatin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Time to reach maximum observed concentration (tmax) of Rosuvastatin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Apparent total body clearance (CL/F) of Rosuvastatin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Rosuvastatin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of AZD0780 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD0780 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Maximum observed plasma concentration (Cmax) of AZD0780 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Time to reach maximum observed concentration (tmax) of AZD0780 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Terminal elimination half-life (t½λz) of AZD0780 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
| Apparent total body clearance (CL/F) of AZD0780 | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose | The effect of AZD0780 on the PK of rosuvastatin in healthy participants will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Adverse Events | From Screening (≤ 28 days to Day -2) until Follow-up Visit (10 to 12 days post-final dose) | The safety and tolerability of AZD0780 in combination with rosuvastatin in healthy participants will be assessed. |
Countries
United States
Outcome results
None listed