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

AstraZeneca

Status and phase: Not yet enrolling; Phase 1

Conditions: Healthy Participants

Treatments: Drug: Erythromycin; Drug: Rosuvastatin; Drug: Simvastatin; Drug: AZD5004; Drug: Atorvastatin; Drug: Repaglinide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06948747

D7260C00017

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 48 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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48 participants in 3 patient groups

Part A

Experimental group

Description:

Participants will receive 10 mg rosuvastatin in Period 1. Participants will receive 10 mg rosuvastatin and AZD5004 in Period 2. Later, participants will receive different doses of AZD5004 followed by 10 mg single dose of rosuvastatin in Period 3, Period 4, Period 5, and Period 6. In Period 7, participants will receive AZD5004 alone and later, 500 mg erythromycin twice a day. Participants will receive 500 mg erythromycin co-administered with AZD5004 during Period 8.

Treatment:

Drug: AZD5004

Drug: Rosuvastatin

Drug: Erythromycin

Part B

Experimental group

Description:

Participants will receive 20 mg simvastatin during Period 1. In Period 2, participants will receive 40mg atorvastatin. In Period 3, participants will receive 40 mg atorvastatin and then, AZD5004 once daily . During Period 4, participants will receive 40 mg atorvastatin with single dose of AZD5004 and later, two different doses of AZD5004 alone will be administered once a day. In Period 5, participants will receive 20 mg simvastatin with single dose of AZD5004, later, AZD5004 alone will be administered once a day. During Period 6, participants will receive 40 mg atorvastatin with single dose of AZD5004 initially, and later AZD5004 will be administered once daily. In Period 7, participants will receive AZD5004 followed by 40 mg single dose of atorvastatin.

Treatment:

Drug: Atorvastatin

Drug: Simvastatin

Drug: AZD5004

Part C

Experimental group

Description:

Participants will receive 0.5 mg repaglinide initially during Period 1, later AZD5004 once daily will be administered . Participants will then receive 0.5 mg repaglinide with single dose of AZD5004 in Period 2, later two different doses of AZD5004 once daily will be administered. In Period 3, participants will receive 0.5 mg repaglinide with single dose of AZD5004 initially, and later AZD5004 once daily will be administered. In Period 4, participants will receive 0.5 mg repaglinide with single dose of AZD5004.

Treatment:

Drug: Repaglinide

Drug: AZD5004