A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD8233 in Healthy Male Subjects With Increased Elevated LDL-C Levels.

Hypercholesterolemia Clinical Trial

Official title: A Phase I Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD8233 Following Single Ascending Dose Administration to Healthy Male Subjects With Elevated LDL-C Levels.

Status Completed

Clinical Trial Summary

AZD8233 has not been evaluated in clinical studies previously. This is a first-in-human (FiH) study. This study will assess the safety, tolerability and pharmacokinetics (PK) of AZD8233, following subcutaneous (SC) administration of single ascending dose (SAD) of AZD8233. This study will also investigate the pharmacodynamics (PD) of AZD8233 by investigating the effect of AZD8233 on levels of cholesterol and related biomarkers.

Clinical Trial Description

This randomized, single-blind, placebo-controlled study will be conducted at a single study center in United States of America. Up to 56 healthy male subjects with elevated LDL-C levels, aged 18 to 60 years will be randomized into this study. This study will consist of 5 cohorts with 8 subjects in each. Depending on emerging data, 2 additional cohorts may be added to test additional dose levels at the discretion of the sponsor, if the pre-defined exposure limits and stopping criteria have not been reached at previous administered doses. The study will comprise of 3 periods:

• A screening period of maximum 28 days.

• A treatment period:

• A follow-up period of 16 weeks

In each cohort, 6 subjects will be randomized to receive a single SC dose of AZD8233 and 2 subjects randomized to receive placebo. Single dose of AZD8233 SC injection (40 mg/mL) will be administered in each cohort as follows:

Cohort 1: Dose 1 (starting dose) Cohort 2: Dose 2 (provisional dose) Cohort 3: Dose 3 (provisional dose) Cohort 4: Dose 4 (provisional dose) Cohort 5: Dose 5 (provisional dose) Dosing for each ascending dose cohort will proceed with 2 subjects in a sentinel cohort, such that 1 subject will be randomized to receive placebo and 1 subject will be randomized to receive AZD8233.

In the treatment period, the sentinel and non-sentinel subjects will be resident at the clinical unit from the day before IMP administration (Day -1) until at least 72 hours and 48 hours after IMP administration, respectively.

Sentinel will have 10 follow-up visits (1, 2, 3, 4, 6, 8, 10, 12, 14 and 16 weeks post-dose). Non-sentinel subjects will have 11 follow-up visits (on Day 4 and 1, 2, 3, 4, 6, 8, 10, 12, 14 and 16 weeks post-dose).

The follow-up period (16 weeks) has been selected based on the predicted terminal half-life of AZD8233 in man (predicted to be 2 to 3 weeks), to cover at least 5 half-lives.

Following review of data from the study, the Safety Review Committee (SRC) may decide to:

• Adjust the window for sentinel dosing.

• Adjust the length of data collection prior to dose-escalation diction.

• Prolong the length of the stay at the Clinical Unit.

• Adjust the timing and number of assessments and/or blood/urine samples for subsequent cohorts.

• Adjust the length of the Follow-up Period. Each subject will be involved in the study for up to 20 weeks. ;

Related Conditions & MeSH terms

• Hypercholesterolemia

• NCT number: NCT03593785
• Study type: Interventional
• Source: AstraZeneca
• Status: Completed
• Phase: Phase 1
• Start date: August 3, 2018
• Completion date: December 19, 2020