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
- Conditions
- Healthy Participants
- Interventions
- Registration Number
- NCT06942936
- Lead Sponsor
- AstraZeneca
- 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
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 38
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:
- 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).
- 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
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: AZD5004 + Itraconazole AZD5004 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. Part A: AZD5004 + Itraconazole 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. Part B: Ethinyl Estradiol/ Levonorgestrel (EE/LNG) + AZD5004 AZD5004 Participants will receive one tablet of combined 0.03/0.15 mg EE/LNG and AZD5004 orally. Part B: Ethinyl Estradiol/ Levonorgestrel (EE/LNG) + AZD5004 EE/LNG Participants will receive one tablet of combined 0.03/0.15 mg EE/LNG and AZD5004 orally.
- Primary Outcome Measures
Name Time Method Part A: Apparent total body clearance (CL/F) of AZD5004 Day 1 and Day 10 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
Part A: Apparent volume of distribution based on the terminal phase (Vz) of AZD5004 Day 1 and Day 10 To assess the effect of multiple doses of itraconazole on the Vz of a single dose of AZD5004 in healthy male and female participants
Part A: Terminal elimination half-life (t1/2λz) of AZD5004 Day 1 and Day 10 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
Part A: Time to reach maximum observed concentration (tmax) of AZD5004 Day 1 and Day 10 To assess the effect of multiple doses of itraconazole on the tmax of a single dose of AZD5004 in healthy male and female participants
Part A: Maximum observed drug concentration (Cmax) of AZD5004 Day 1 and Day 10 To assess the effect of multiple doses of itraconazole on the Cmax of a single dose of AZD5004 in healthy male and female participants
Part A: Area under concentration-time curve from time zero to infinity (AUCinf) of AZD5004 Day 1 and Day 10 To assess the effect of multiple doses of itraconazole on the AUCinf of a single dose of AZD5004 in healthy male and female participants.
Part A: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of AZD5004 Day 1 and Day 10 To assess the effect of multiple doses of itraconazole on the AUClast of a single dose of AZD5004 in healthy male and female participants
Part B: Area under concentration-time curve from time zero to infinity (AUCinf) of EE/LNG Day 1, Day 8, Day 50 and Day 78 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
Part B: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of EE/LNG Day 1, Day 8, Day 50 and Day 78 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
Part B: Maximum observed drug concentration (Cmax) of EE/LNG Day 1, Day 8, Day 50 and Day 78 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
Part B: Terminal elimination half-life (t1/2λz) of EE/LNG Day 1, Day 8, Day 50 and Day 78 To assess the effect of single and multiple oral doses of AZD5004, at different dose levels of AZD5004, on the t1/2λz of single doses of combined oral EE/LNG in healthy female participants
Part B: Time to reach maximum observed concentration (tmax) of EE/LNG Day 1, Day 8, Day 50 and Day 78 To assess the effect of single and multiple oral doses of AZD5004, at different dose levels of AZD5004, on the tmax of single doses of combined oral EE/LNG in healthy female participants
Part B: Apparent total body clearance (CL/F) of EE/LNG Day 1, Day 8, Day 50 and Day 78 To assess the effect of single and multiple oral doses of AZD5004, at different dose levels of AZD5004, on the CL/F of single doses of combined oral EE/LNG in healthy female participants
Part B: Apparent volume of distribution based on the terminal phase (Vz) of EE/LNG Day 1, Day 8, Day 50 and Day 78 To assess the effect of single and multiple oral doses of AZD5004, at different dose levels of AZD5004, on the Vz of single doses of combined oral EE/LNG in healthy female participants
- Secondary Outcome Measures
Name Time Method Part B: Number of patients with AEs From Screening (Day -2 to Day -28) to Day 96 To assess the safety and tolerability of AZD5004 alone and in combination with combined oral EE/LNG in healthy female participants
Part A: Number of patients with Adverse Events (AEs) From Screening (Day -2 to Day -28) to Day 27 To assess the safety and tolerability of AZD5004 alone and in combination with itraconazole in healthy male and female participants
Part B: AUCinf of AZD5004 Days 8, Day 50 and Day 78 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.
Part B: AUClast of AZD5004 Days 8, Day 50 and Day 78 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
Part B: Cmax of AZD5004 Day 8, Day 50 and Day 78 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
Trial Locations
- Locations (1)
Research Site
🇩🇪Berlin, Germany