Clinical trial NCT05787002: A Study to Assess the Effect of AZD0780 on the Pharmacokinetics of Rosuvastatin.
Official title: An Open-label, 2-Period, 2-Sequence Cross-over Study to Assess the Effect of AZD0780 on the Pharmacokinetics of Rosuvastatin in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dyslipidemia
Keywords: Hypercholesterolemia
elevated Low-density lipoprotein-cholesterol (LDL-C) levels
Drug-drug interaction
Healthy Participants
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-03-28
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) of Rosuvastatin
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast) of Rosuvastatin
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Maximum observed plasma concentration (Cmax) of Rosuvastatin
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Terminal elimination half-life (t½λz) of Rosuvastatin
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Time to reach maximum observed concentration (tmax) of Rosuvastatin
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Apparent total body clearance (CL/F) of Rosuvastatin
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Rosuvastatin
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) of AZD0780
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD0780
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Maximum observed plasma concentration (Cmax) of AZD0780
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Time to reach maximum observed concentration (tmax) of AZD0780
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Terminal elimination half-life (t½λz) of AZD0780
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Apparent total body clearance (CL/F) of AZD0780
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
measure: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD0780
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose
Secondary outcomes:
measure: Number of participants with Adverse Events
timeFrame: From Screening (≤ 28 days to Day -2) until Follow-up Visit (10 to 12 days post-final dose)
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: