A Study to Investigate the Impact of Multiple Doses of Itraconazole on AZD5004 in Healthy Participants and Multiple Doses of AZD5004 on Combined Oral Ethinyl Oestradiol and Levonorgestrel in Healthy Female Participants

AstraZeneca

Status and phase: Begins enrollment this month; Phase 1

Conditions: Healthy Participants

Treatments: Drug: EE/LNG; Drug: Itraconazole; Drug: AZD5004

Study type: Interventional

Funder types: Industry

Identifiers

NCT06942936

D7260C00007

2024-518467-35-00 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to assess the impact of multiple doses of itraconazole on the pharmacokinetics (PK) of AZD5004 in healthy participants (Part A), and to assess the impact of multiple doses of AZD5004 on the PK of Combined Oral Contraceptives (COCs) in healthy female participants (Part B).

Full description

This study will be an open-label, fixed-sequence, two-part study in healthy participants.

There are 2 parts in this study:

Part A: performed in healthy male and female participants. Part B: performed in healthy female participants of non-childbearing potential.

Part A will consist of:

1. Screening period of 27 days
2. Period 1
3. Period 2
4. Period 3
5. Follow-up period of 17 to 24 days after the last AZD5004 dose

Part B will consist of:

1. Screening period of 27 days
2. Start of study period
3. Up-titration period
4. End of study period
5. Follow-up

Enrollment: 38 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Main Inclusion Criteria:

Part A -

• Suitable veins for cannulation or repeated venipuncture.
• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
• Females of childbearing potential must not be lactating, must agree to use approved method of contraceptive.
• Sexually active fertile male participants with female partners of childbearing potential must adhere to the approved contraception methods.
• Have a Body Mass Index (BMI) between ≥ 18.5 kg/m2 and ≤ 35 kg/m2 (at the time of screening) and weigh at least 50 kg.

Part B -

• Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria:

  1. Postmenopausal defined as amenorrhoea for at least 12 months following cessation of all exogenous hormonal treatments and Follicle-stimulating hormone (FSH) levels (> 40 mIU/mL).
  2. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation or tubal occlusion.

• Have a BMI between ≥ 23 kg/m2 and ≤ 35 kg/m2 and weigh at least 55 kg.

Main Exclusion Criteria:

Part A and Part B-

• History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study.
• History of acute pancreatitis (unless due to previously resolved gallstone pancreatitis and post-cholecystectomy), chronic pancreatitis, gallstones, or elevation in serum lipase/pancreatic amylase.
• History or presence of 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.
• Abnormal laboratory values, hepatic disease, Human Immunodeficiency Virus (HIV) positive, abnormal vital signs, abnormalities in rhythm, uncontrolled thyroid disease.
• Known smoker, history of alcohol, drug abuse or caffeine intake.
• Use of prescribed or unsubscribed medication within 3 months prior to screening.
• History of psychosis, bipolar disorder, major depressive disorder.
• Vulnerable participants, e.g., kept in detention, protected adults under guardianship.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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38 participants in 2 patient groups

Part A: AZD5004 + Itraconazole

Experimental group

Description:

Participants will receive oral dose of AZD5004 on Period 1, followed by Itraconazole capsule orally in Period 2, and then will receive oral dose of AZD5004 combination with Itraconazole capsule in Period 3.

Treatment:

Drug: AZD5004

Drug: Itraconazole

Part B: Ethinyl Estradiol/ Levonorgestrel (EE/LNG) + AZD5004

Experimental group

Description:

Participants will receive one tablet of combined 0.03/0.15 mg EE/LNG and AZD5004 orally.

Treatment:

Drug: AZD5004

Drug: EE/LNG