A Study to Investigate the Effect of AZD5004 on Rosuvastatin, Atorvastatin, Simvastatin, Repaglinide and the Effect of Erythromycin on AZD5004 in Healthy Participants

AstraZeneca49 enrolled

Overview

This study will assess the effect of AZD5004 on Rosuvastatin, Atorvastatin, Simvastatin, Repaglinide and the effect of Erythromycin on AZD5004 in healthy adult male and female participants.

This is a Phase I, open-label, fixed-sequence, single center study which consists of 3 parts: Part A, Part B and Part C. Part A, Part B, and Part C are 3 independent and non-sequential parts in this study. The purpose of Part A (Rosuvastatin and Erythromycin) of this study is to measure the following in healthy male and female participants, 1. The impact of AZD5004 on the pharmacokinetics (PK: the way the body absorbs, distributes, metabolizes, and eliminates a medicine) of rosuvastatin and 2. The impact of erythromycin on the PK of AZD5004 The purpose of Part B (Atorvastatin and Simvastatin) of this study is to measure the impact of AZD5004 on the PK of atorvastatin and simvastatin in healthy male and female participants. The purpose of Part C (Repaglinide) of this study is to measure the impact of AZD5004 on the PK of repaglinide in healthy male and female participants. Part A will consist of a screening period, 8 treatment periods, and a follow-up period. Part B will consist of a screening period, 7 treatment periods, and a follow-up period. Part C will consist of a screening period, 4 treatment periods, and a follow-up period.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy Participants

Interventions

AZD5004DRUG

Participants will receive oral tablets of AZD5004 as single dose on the following days, (i) Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 and Day 55 in Part A. (ii) Day 9 to Day15, Day 16, Day 17 to Day 23, Day 24 to Day 30, Day 31 to Day 37, Day 38 to Day 41 and Day 42 in Part B. (iii) Day 3 to Day 9, Day 10 to Day 25, Day 26 to Day 33, and Day 34 in Part C.

RosuvastatinDRUG

Participants will receive single oral tablets of rosuvastatin 10mg on Days 1, 7, 14, 21, 28, and 35.

ErythromycinDRUG

Participants will receive oral doses of erythromycin 500 mg, twice a day from Day 49 to Day 54; and a single dose of 500 mg on Day 55.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy male and female participants aged 18 to 55 years * All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit. * Female(s) of childbearing potential if heterosexually active, must agree to use an approved method of highly effective contraception. * Male participants must use condoms for the duration of clinical trial. * Additional contraception must be used for the sexual partners of male trial participants throughout the clinical trial. * Have a body mass index (BMI) between ≥ 20.0 and ≤ 35 kg/m2 (at the time of screening) inclusive and weigh at least 50 kg. Exclusion Criteria: * History of any clinically important disease or disorder (liver transplant, liver disease, positive for serum HBsAg (Hepatitis B surface antigen) OR anti-HBcAb (Hepatitis B core antibody), positive for anti-HCV (Hepatitis C virus), history of cirrhosis and/or hepatic decompensation, cardiovascular disease, neuromuscular or neurogenic disease. * History of Type 1 or Type 2 diabetes mellitus (DM). * History of Hemoglobin A1c ≥ 6.5% (≥ 48 mmol/mol) at screening. * 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. * Any laboratory values with deviations or clinically important abnormalities in clinical chemistry, hematology, or urinalysis at the Screening Visit or on admission to the Clinical Unit. * Significant hepatic disease as judged by the investigator. * Any positive result on screening for serum HBsAg, HBcAb or HIV (Human immunodeficiency virus). * Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12 lead ECG, at screening * Abnormal vital signs. * Uncontrolled thyroid disease or history/family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2). * Current smokers or those who have smoked or used nicotine products. * Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the investigator. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g of alcohol per day for females. * Positive screen for drugs of abuse, or alcohol or cotinine at screening or on each admission to the Clinical Unit. * History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity. * Excessive intake of caffeine-containing drinks or food * History of psychosis or bipolar disorder or major depressive disorder or suicide attempt or suicidal ideation.

Locations (1)

Research Site

Brooklyn, Maryland, United States

Outcomes

Primary Outcomes

Part A, Part B and Part C: Area under concentration time curve from time 0 to infinity (AUCinf)

Part A: To assess the effect of single dose of AZD5004 on the PK of a single dose of rosuvastatin and multiple doses of erythromycin on the PK of a single dose of AZD5004 in healthy participants. Part B: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of atorvastatin and atorvastatin metabolites (o-hydroxy atorvastatin and p-hydroxy atorvastatin) and simvastatin and simvastatin metabolites (simvastatin acid) in healthy participants. Part C: To assess the effect of multiple doses of AZD5004 on the PK of a single dose of repaglinide in healthy participants.

Time frame: Part A:Days 1-4, 7-10, 14-17, 21-24, 28-31, 35-38, 42-49 and 55-62 Part B:Days 1, 2, 4-7, 8-11, 15, 16-19, 23, 24, 30, 31, 32, 37, 38-41, 42-45 Part C:Days 1, 2, 9, 10, 11, 18, 19, 25, 26, 27, 33, 34-36

Part A, Part B and Part C: Area under concentration curve from time 0 to the last quantifiable concentration (AUClast)

Part A, Part B and Part C: Maximum observed drug concentration (Cmax)

Data from ClinicalTrials.gov

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