Healthy
Conditions
Keywords
Pharmacokinetics, Cardiorenal diseases, Cryopyrin, Drug-drug interaction
Brief summary
The purpose of the study is to assess the pharmacokinetics (PK) of AZD4144 when administered alone and in combination with itraconazole in healthy participants.
Detailed description
This is an open-label, randomised, two arm, 3 period, fixed sequence study in healthy participants. The study will include two parallel, independent arms with one arm evaluating oral administration of AZD4144 and the other evaluating AZD4144 administered as an intravenous (IV) infusion. Each study arm will comprise of: 1. A screening period of up to 28 days. 2. Three treatment periods during which participants will receive AZD4144 alone, itraconazole alone, and AZD4144 in combination with itraconazole. 3. A final follow-up visit.
Interventions
DRUGAZD4144
AZD4144 will be administered orally.
DRUGItraconazole
Itraconazole will be administered orally.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and/or female participants with suitable veins for cannulation or repeated venipuncture. 2. Body mass index (BMI) between 18.0 and 30.0 kg/m², inclusive, and body weight of at least 50 kg. 3. Female participants of childbearing potential must have a negative serum or urine pregnancy test and must agree to use highly effective contraception throughout the study and follow-up period. 4. Male participants must agree to use adequate contraception and refrain from sperm donation during the study and for the protocol-specified period after the last dose.
Exclusion criteria
1. Any clinically significant disease or medical condition that may interfere with study participation or interpretation of results. 2. History or presence of gastrointestinal, hepatic, renal or any other condition known to interfere absorption, distribution, metabolism, or excretion of study drugs. 3. Any clinically important illness, medical/surgical procedure, or trauma. 4. Active systemic bacterial, viral, or fungal infection. 5. Clinically significant serious active or chronic infections. 6. Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection. 7. Concomitant immunosuppressive, steroid treatment. 8. Clinically significant abnormalities in physical examination, vital signs, 12-lead electrocardiogram (ECG), or clinical laboratory assessments. 9. Known hypersensitivity or allergy to AZD4144, itraconazole, or any excipients of the study interventions. 10. Positive screening test for drugs of abuse, alcohol, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under concentration time curve from time 0 to infinity (AUCinf) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To assess the effect of itraconazole on the PK (AUCinf) of AZD4144 |
| Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To assess the effect of itraconazole on the PK (AUClast) of AZD4144 |
| Maximum observed drug concentration (Cmax) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To assess the effect of itraconazole on the PK (Cmax) of AZD4144 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total body clearance (CL) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To describe the PK (CL) of AZD4144 when administered alone, and in combination with itraconazole |
| Apparent total body clearance (CL/F) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To describe the PK (CL/F) of AZD4144 when administered alone, and in combination with itraconazole |
| Volume of distribution during the terminal phase (Vz) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To describe the PK (Vz) of AZD4144 when administered alone, and in combination with itraconazole |
| Apparent volume of distribution based on the terminal phase (Vz/F) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To describe the PK (Vz/F) of AZD4144 when administered alone, and in combination with itraconazole |
| Terminal elimination half life (t½λz) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To describe the PK (t½λz) of AZD4144 when administered alone, and in combination with itraconazole |
| Time to reach maximum observed concentration (tmax) | Period 1: Day 1 to Day 6; Period 3: Day 10 to Day 16 | To describe the PK (tmax) of AZD4144 when administered alone, and in combination with itraconazole |
Countries
United Kingdom
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed