Healthy Participants
Conditions
Keywords
Obesity, Type 2 Diabetes
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. 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
Interventions
Sponsors
AstraZeneca
Parexel
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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. Part B will be performed in healthy female participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion 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 ≤ 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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: 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: 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 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 dosing 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 dosing 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 dosing 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 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 |
| 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 dosing 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 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 |
| 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 dosing of AZD5004, at different dose levels of AZD5004, on the Vz of single doses of combined oral EE/LNG in healthy female participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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 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 |
Countries
Germany, United States
Outcome results
None listed