Healthy Participants
Conditions
Keywords
Pharmacokinetics, Drug-drug interaction, Dyslipidemias, Hypercholesterolemia, Lipoprotein (a)
Brief summary
The purpose this study is to measure the impact of laroprovstat (AZD0780) on the pharmacokinetics (PK) of AZD4954 and the impact of AZD4954 on the PK of laroprovstat in healthy male and female participants.
Detailed description
This is an open-label, fixed-sequence, 2 period and 2 cohort study in healthy participants. Each participant in each cohort will receive treatments in a fixed order during the 2 treatment periods as follows: * Cohort 1: Treatment A followed by Treatment C. * Cohort 2: Treatment B followed by Treatment C. The following treatments will be given during the study: * Treatment A: single dose of AZD4954 alone. * Treatment B: single dose of laroprovstat alone. * Treatment C: single doses of laroprovstat + AZD4954. The study will comprise of a Screening Period, two Treatment Periods and follow-up visits.
Interventions
DRUGAZD4954
AZD4954 will be administered orally.
DRUGLaroprovstat
Laroprovstat will be administered orally.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* All females must have a negative pregnancy test at the Screening Visit. * Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception. * Females of non-childbearing potential must be confirmed as postmenopausal or have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion. * Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods. * Have a body mass index between 18 and 35 kg/m2 inclusive and weigh at least 50 kg.
Exclusion criteria
* History of any clinically important disease or disorder. * History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. * Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention. * Participants with known bleeding or coagulation disorders. * Any clinically important abnormalities in laboratory values, clinical chemistry, hematology, urinalysis results, or vital signs. * Any positive result on Screening for serum hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). * Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead electrocardiogram at screening. * Participants who are current smokers or have used any tobacco or nicotine-containing products (including e-cigarettes) within 3 months prior to screening; known or suspected history of alcohol or drug abuse; positive screen for drugs of abuse, alcohol, or cotinine at screening or on each admission to the Clinical Unit. * History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity or history of hypersensitivity to drugs of a similar chemical structure or class to AZD4954 or laroprovstat. * Participants who have previously received AZD4954. * Treatment with any lipid-lowering therapy or laroprovstat within the 3 months prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under concentration time curve from time 0 to infinity (AUCinf) of AZD4954 | Cohort 1: Day 1 to Day 41 | To assess the effect of a single dose of oral laroprovstat on the PK of a single dose of oral AZD4954 in healthy participants. |
| Maximum observed drug concentration (Cmax) of AZD4954 | Cohort 1: Day 1 to Day 41 | To assess the effect of a single dose of oral laroprovstat on the PK of a single dose of oral AZD4954 in healthy participants. |
| AUCinf of laroprovstat | Cohort 2: Day 1 to Day 25 | To assess the effect of a single dose of oral AZD4954 on the PK of a single dose of oral laroprovstat in healthy participants. |
| Cmax of laroprovstat | Cohort 2: Day 1 to Day 25 | To assess the effect of a single dose of oral AZD4954 on the PK of a single dose of oral laroprovstat in healthy participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) of AZD4954 | Cohort 1: Day 1 to Day 41; Cohort 2: Day 11 to Day 31 | To describe the PK of AZD4954 when administered alone and in combination with laroprovstat. |
| Apparent total body clearance (CL/F) of AZD4954 | Cohort 1: Day 1 to Day 41; Cohort 2: Day 11 to Day 31 | To describe the PK of AZD4954 when administered alone and in combination with laroprovstat. |
| Terminal elimination half-life (t½λz) of AZD4954 | Cohort 1: Day 1 to Day 41; Cohort 2: Day 11 to Day 31 | To describe the PK of AZD4954 when administered alone and in combination with laroprovstat. |
| Time to reach maximum observed concentration (tmax) of AZD4954 | Cohort 1: Day 1 to Day 41; Cohort 2: Day 11 to Day 31 | To describe the PK of AZD4954 when administered alone and in combination with laroprovstat. |
| Time of last quantifiable concentration (tlast) of AZD4954 | Cohort 1: Day 1 to Day 41; Cohort 2: Day 11 to Day 31 | To describe the PK of AZD4954 when administered alone and in combination with laroprovstat. |
| Time delay between drug administration and the first observed concentration (tlag) of AZD4954 | Cohort 1: Day 1 to Day 41; Cohort 2: Day 11 to Day 31 | To describe the PK of AZD4954 when administered alone and in combination with laroprovstat. |
| Apparent volume of distribution based on the terminal phase (Vz/F) of AZD4954 | Cohort 1: Day 1 to Day 41; Cohort 2: Day 11 to Day 31 | To describe the PK of AZD4954 when administered alone and in combination with laroprovstat. |
| AUClast of laroprovstat | Cohort 1: Day 21 to Day 35; Cohort 2: Day 1 to Day 25 | To describe the PK of laroprovstat when administered alone and in combination with AZD4954. |
| CL/F of laroprovstat | Cohort 1: Day 21 to Day 35; Cohort 2: Day 1 to Day 25 | To describe the PK of laroprovstat when administered alone and in combination with AZD4954. |
| t½λz of laroprovstat | Cohort 1: Day 21 to Day 35; Cohort 2: Day 1 to Day 25 | To describe the PK of laroprovstat when administered alone and in combination with AZD4954. |
| tmax of laroprovstat | Cohort 1: Day 21 to Day 35; Cohort 2: Day 1 to Day 25 | To describe the PK of laroprovstat when administered alone and in combination with AZD4954. |
| tlast of laroprovstat | Cohort 1: Day 21 to Day 35; Cohort 2: Day 1 to Day 25 | To describe the PK of laroprovstat when administered alone and in combination with AZD4954. |
| tlag of laroprovstat | Cohort 1: Day 21 to Day 35; Cohort 2: Day 1 to Day 25 | To describe the PK of laroprovstat when administered alone and in combination with AZD4954. |
| Vz/F of laroprovstat | Cohort 1: Day 21 to Day 35; Cohort 2: Day 1 to Day 25 | To describe the PK of laroprovstat when administered alone and in combination with AZD4954. |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Cohort 1: Up to Day 83; Cohort 2: Up to Day 73 | To assess the safety and tolerability of AZD4954 alone and in combination with laroprovstat; and safety and tolerability of laroprovstat alone and in combination with AZD4954 following oral administration of single doses in healthy participants. |
Countries
United States
Outcome results
None listed