Clinical trial NCT06942936: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Obesity
Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-04-24
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A and Part B are 2 independent and non-sequential parts (arms) in this study. Part A will be performed in healthy male and female participants in Germany. Part B will be performed in healthy female participants of non-childbearing potential in Germany and in the USA.
Primary purpose: TREATMENT

Brief summary: 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).

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 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

Eligibility 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.

Primary outcomes:
measure: Part A: Area under concentration-time curve from time zero to infinity (AUCinf) of AZD5004
timeFrame: Day 1 and Day 10
measure: Part A: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of AZD5004
timeFrame: Day 1 and Day 10
measure: Part A: Maximum observed drug concentration (Cmax) of AZD5004
timeFrame: Day 1 and Day 10
measure: Part A: Terminal elimination half-life (t1/2λz) of AZD5004
timeFrame: Day 1 and Day 10
measure: Part A: Time to reach maximum observed concentration (tmax) of AZD5004
timeFrame: Day 1 and Day 10
measure: Part A: Apparent total body clearance (CL/F) of AZD5004
timeFrame: Day 1 and Day 10
measure: Part A: Apparent volume of distribution based on the terminal phase (Vz) of AZD5004
timeFrame: Day 1 and Day 10
measure: Part B: Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG
timeFrame: Day 1, Day 8, Day 50 and Day 78
measure: Part B: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of EE/LNG
timeFrame: Day 1, Day 8, Day 50 and Day 78
measure: Part B: Maximum observed drug concentration (Cmax) of EE/LNG
timeFrame: Day 1, Day 8, Day 50 and Day 78
measure: Part B: Terminal elimination half-life (t1/2λz) of EE/LNG
timeFrame: Day 1, Day 8, Day 50 and Day 78
measure: Part B: Time to reach maximum observed concentration (tmax) of EE/LNG
timeFrame: Day 1, Day 8, Day 50 and Day 78
measure: Part B: Apparent total body clearance (CL/F) of EE/LNG
timeFrame: Day 1, Day 8, Day 50 and Day 78
measure: Part B: Apparent volume of distribution based on the terminal phase (Vz) of EE/LNG
timeFrame: Day 1, Day 8, Day 50 and Day 78
Secondary outcomes:
measure: Part A: Number of patients with Adverse Events (AEs)
timeFrame: From Screening (Day -2 to Day -28) to Day 27
measure: Part B: Number of patients with AEs
timeFrame: From Screening (Day -2 to Day -28) to Day 96
measure: Part B: AUCinf of AZD5004
timeFrame: Days 8, Day 50 and Day 78
measure: Part B: AUClast of AZD5004
timeFrame: Days 8, Day 50 and Day 78
measure: Part B: Cmax of AZD5004
timeFrame: Day 8, Day 50 and Day 78
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Berlin
country: Germany
facility: Research Site
Study officials:
References: