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

An Open-label, Fixed-sequence and Two-part Study to Assess the Impact of Multiple Doses of Itraconazole on the Pharmacokinetics of AZD5004 in Healthy Participants and Multiple Doses of AZD5004 on the Pharmacokinetics of Combined Oral Ethinyl Oestradiol and Levonorgestrel in Healthy Female Participants

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).

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD5004; Drug: Itraconazole; Drug: EE/LNG

Detailed 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.

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

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Research Site
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 ≤ 30 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 at screening.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: AZD5004 + Itraconazole; 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.	Drug: AZD5004; AZD50004 is administered orally as a tablet.; Drug: Itraconazole; Itraconazole is administered orally as a capsule.
Experimental: Part B: Ethinyl Estradiol/ Levonorgestrel (EE/LNG) + AZD5004; Participants will receive one tablet of combined 0.03/0.15 mg EE/LNG and AZD5004 orally.	Drug: AZD5004; AZD50004 is administered orally as a tablet.; Drug: EE/LNG; EE/LNG is administered orally in the form of tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Area under concentration-time curve from time zero to infinity (AUCinf) of AZD5004	To assess the effect of multiple doses of itraconazole on the AUCinf of a single dose of AZD5004 in healthy male and female participants.	Day 1 and Day 10
Part A: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of AZD5004	To assess the effect of multiple doses of itraconazole on the AUClast of a single dose of AZD5004 in healthy male and female participants	Day 1 and Day 10
Part A: Maximum observed drug concentration (Cmax) of AZD5004	To assess the effect of multiple doses of itraconazole on the Cmax of a single dose of AZD5004 in healthy male and female participants	Day 1 and Day 10
Part A: Terminal elimination half-life (t1/2λz) of AZD5004	To assess the effect of multiple doses of itraconazole on the t1/2λz of a single dose of AZD5004 in healthy male and female participants	Day 1 and Day 10
Part A: Time to reach maximum observed concentration (tmax) of AZD5004	To assess the effect of multiple doses of itraconazole on the tmax of a single dose of AZD5004 in healthy male and female participants	Day 1 and Day 10
Part A: Apparent total body clearance (CL/F) of AZD5004	To assess the effect of multiple doses of itraconazole on the CL/F of a single dose of AZD5004 in healthy male and female participants	Day 1 and Day 10
Part A: Apparent volume of distribution based on the terminal phase (Vz) of AZD5004	To assess the effect of multiple doses of itraconazole on the Vz of a single dose of AZD5004 in healthy male and female participants	Day 1 and Day 10
Part B: Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG	To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the AUCinf of single doses of combined oral EE/LNG in healthy female participants	Day 1, Day 8, Day 50 and Day 78
Part B: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of EE/LNG	To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the AUClast of single doses of combined oral EE/LNG in healthy female participants	Day 1, Day 8, Day 50 and Day 78
Part B: Maximum observed drug concentration (Cmax) of EE/LNG	To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the Cmax of single doses of combined oral EE/LNG in healthy female participants	Day 1, Day 8, Day 50 and Day 78
Part B: Terminal elimination half-life (t1/2λz) of EE/LNG	To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the t1/2λz of single doses of combined oral EE/LNG in healthy female participants	Day 1, Day 8, Day 50 and Day 78
Part B: Time to reach maximum observed concentration (tmax) of EE/LNG	To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the tmax of single doses of combined oral EE/LNG in healthy female participants	Day 1, Day 8, Day 50 and Day 78
Part B: Apparent total body clearance (CL/F) of EE/LNG	To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the CL/F of single doses of combined oral EE/LNG in healthy female participants	Day 1, Day 8, Day 50 and Day 78
Part B: Apparent volume of distribution based on the terminal phase (Vz) of EE/LNG	To assess the effect of single and multiple oral dosing of AZD5004, at different dose levels of AZD5004, on the Vz of single doses of combined oral EE/LNG in healthy female participants	Day 1, Day 8, Day 50 and Day 78

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of patients with Adverse Events (AEs)	To assess the safety and tolerability of AZD5004 alone and in combination with itraconazole in healthy male and female participants	From Screening (Day -2 to Day -28) to Day 27
Part B: Number of patients with AEs	To assess the safety and tolerability of AZD5004 alone and in combination with combined oral EE/LNG in healthy female participants	From Screening (Day -2 to Day -28) to Day 96
Part B: AUCinf of AZD5004	To assess the effect of single and multiple oral doses of AZD5004, at different dose levels of AZD5004, on the AUCinf of single doses of combined oral EE/LNG in healthy female participants.	Days 8, Day 50 and Day 78
Part B: AUClast of AZD5004	To assess the effect of single and multiple oral doses of AZD5004, at different dose levels of AZD5004, on the AUClast of single doses of combined oral EE/LNG in healthy female participants	Days 8, Day 50 and Day 78
Part B: Cmax of AZD5004	To assess the effect of single and multiple oral doses of AZD5004, at different dose levels of AZD5004, on the Cmax of single doses of combined oral EE/LNG in healthy female participants	Day 8, Day 50 and Day 78

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2025
• Primary Completion (Actual): January 28, 2026
• Study Completion (Actual): January 28, 2026

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 17, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Type 2 Diabetes
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Triazoles; Piperazines; Itraconazole
• Other Study ID Numbers: D7260C00007; 2024-518467-35-00 (Other Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No