NCT05384262

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD0780 in Healthy Subjects

A Phase I, Randomized, Single-Blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD0780 Following Single and Multiple Ascending Dose Administration to Healthy Subjects With or Without Elevated LDL-C Levels

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 183 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD0780 following single and multiple dose administration to healthy subjects with or without elevated Low-Density Lipoprotein-Cholesterol (LDL-C) levels. This study will consist of two parts (Parts A and B). 56 subjects have been planned for Part A and 141 subjects for Part B. Additional subjects may be included for the optional cohorts depending upon emerging data.

Detailed description

This is a Phase I, First In Human (FIH), randomized, single-blind, placebo-controlled, study in healthy male and/or female subjects of non-childbearing potential including healthy subjects of Chinese and Japanese ethnicity performed at multiple centers (up to 4 study centers). 56 subjects have been planned for Part A and 141 subjects for Part B. * Part A: * A Screening Period of maximum 28 days. * Admission to study center (Day -1 or Day -2). * A Treatment Period (Day 1 to Day 3) with a single dose of AZD0780 or placebo on Day 1. Subjects will be discharged on Day 3. * A Follow-up Visit within 5 to 7 days after the Investigational Medicinal Product (IMP) dose for all cohorts. * An additional Follow-up Visit within 9 to 11 days after the IMP dose from Cohort 3 onwards. (i) Part A1 - Up to 5 dose cohorts of AZD0780 are planned to be investigated. Depending on the findings, up to 4 additional dose cohorts may be added. Within each cohort, 6 subjects will be randomized to receive AZD0780, and 2 subjects randomized to receive placebo. Dosing for each ascending dose cohort will proceed with 2 subjects in a sentinel sub-cohort such that one subject will be randomized to receive AZD0780, and one subject will be randomized to receive placebo. (ii) Part A2 - The subjects from a chosen cohort in Part A1 will return to the study center no sooner than 9 days after the first dose administration of IMP and will receive AZD0780 or placebo after intake of a high-calorie, high-fat breakfast, to assess the effect of food on the PK of AZD0780. The subjects will stay at the study center until 48 hours post-dose in both the parts. • Part B: * Global Multiple Ascending Dose (MAD) cohort - Up to 3 dose cohorts are planned to be investigated. In each cohort, 20 subjects will participate and receive either AZD0780 or placebo, randomized 3:1 for 28 days dosing. Depending on the findings, 3 additional dose levels may be added in up to 3 additional cohorts (up to 20 subjects per cohort). * Japanese Single and Multiple Ascending Dose (JSMAD) cohorts - Two cohorts are planned. One cohort of 8 Japanese subjects will receive a medium dose level of AZD0780 or placebo randomized 3:1 for 9 days dosing (subjects will receive a single dose of IMP on Day 1 followed by daily dosing on Days 8 to 15 \[there is no dose on Days 2 to 7\]). The second cohort of 8 Japanese subjects will receive a higher dose level of AZD0780 or placebo. * Rosuvastatin global MAD cohorts - Two cohorts are planned. Up to 40 subjects in the first cohort will receive either AZD0780 in combination with rosuvastatin or placebo in combination with rosuvastatin, randomized 1:1 to 1 of the 2 treatment arms with 20 subjects per arm. Up to 25 subjects will participate in the second cohort and will be randomized 4:1 to 1 of 2 treatment arms to receive either AZD0780 in combination with rosuvastatin (20 subjects) or placebo in combination with rosuvastatin (5 subjects). Subjects eligible for these cohorts will begin a Screening period of 56 days, a minimum of 21 days run-in period (maximum of up to 28 days), Treatment period of 28 days for each cohort and two Follow-up visits (1 \& 2 weeks after last dose of IMP).

Conditions

• Dyslipidemia

Interventions

Type	Name	Description
DRUG	AZD0780	Subjects will receive AZD0780 orally as a single ascending dose.
DRUG	AZD0780	Subjects will receive AZD0780 orally as a multiple ascending dose.
DRUG	AZD0780	Subjects will receive AZD0780 orally as a single and multiple ascending dose.
DRUG	Placebo	Subjects will receive placebo matching the AZD0780 dose orally as a single ascending dose.
DRUG	Placebo	Subjects will receive placebo matching the AZD0780 dose orally as a multiple ascending dose.
DRUG	Placebo	Subjects will receive placebo matching the AZD0780 dose orally as a single and multiple ascending dose.
DRUG	Rosuvastatin	Subjects will receive rosuvastatin orally.

Timeline

• Start date: 2022-05-18
• Primary completion: 2024-06-14
• Completion: 2024-06-14
• First posted: 2022-05-20
• Last updated: 2024-07-19

Locations

3 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study