An open-label, fixed sequence study in healthy participants to assess the pharmacokinetics of AZD0780 when administered alone and in combination with itraconazole and carbamazepine, and to assess the pharmacokinetics of midazolam and ethinyl estradiol/levonorgestrel (EE and LNG) when administered alone and in combination with AZD0780.
The purpose of this study is to quantify the effect of itraconazole, a strong CYP3A inhibitor, and carbamazepine, a strong CYP3A inducer, on the PK of AZD0780 in healthy participants. This study will also evaluate AZD0780 as a precipitant of CYP3A4 mediated DDI by examining the PK of midazolam (a CYP3A4 substrate) and EE and LNG (CYP3A4 substrates) alone and in combination with AZD0780 in healthy participants. The study duration (including screening period) will be approximately 9 to 10 weeks for Part 1, 12 to 14 weeks for Part 2, 6 to 8 weeks for Part 3, and 8 to 10 weeks for Part 4 (optional). Study visits and treatment: * Part 1: Participants who are eligible to participate in this study will stay at the Clinical Unit from Day -1 to Day 24 and return to the Clinical Unit again for a Follow-up Visit, 7 to 14 days after the last PK sample. * Part 2: Participants who are eligible to participate in this study will stay at the Clinical Unit from Day -1 to Day 37 and return to the Clinical Unit again for a Follow-up Visit, 7 to 14 days after the last PK sample. * Part 3: Participants who are eligible to participate in this study will stay at the Clinical Unit from Day -1 to Day 12 and return to the Clinical Unit again for a Follow-up Visit, 7 to 14 days after the last PK sample. * Part 4 (optional): Participants who are eligible to participate in this study will stay at the Clinical Unit from Day -1 to Day 22 and return to the Clinical Unit again for a Follow-up Visit, 7 to 14 days after the last PK sample. Number of Participants: Approximately 78 participants will be enrolled in this study; 18 participants in Part 1 (itraconazole Cohort), 24 participants in Part 2 (carbamazepine Cohort), 18 participants in Part 3 (midazolam Cohort), and 18 Participants in Part 4 (EE and LNG Cohort) (optional).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
59
Dose 1 and Dose 2
* Period 2 (itraconazole administration only). * Period 3 (AZD0780 + itraconazole administration).
* Period 2 (carbamazepine administration only). * Period 3 (AZD0780 + carbamazepine administration only).
Research Site
Brooklyn, Maryland, United States
AUCinf (Area under concentration-time curve from time 0 to infinity)
To describe the PK of AZD0780 when administered alone and in combination with itraconazole and carbamazepine.
Time frame: Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)
AUClast (Area under concentration curve from time 0 to the last quantifiable concentration)
To describe the PK of AZD0780 when administered alone and in combination with itraconazole and carbamazepine.
Time frame: Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)
Cmax (Maximum observed drug concentration)
To describe the PK of AZD0780 when administered alone and in combination with itraconazole and carbamazepine.
Time frame: Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)
AUCinf
To assess the effect of AZD0780 on the PK of midazolam (Part 3) and EE and LNG (Part 4).
Time frame: Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)
AUClast
To assess the effect of AZD0780 on the PK of midazolam (Part 3) and EE and LNG (Part 4).
Time frame: Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)
Cmax
To assess the effect of AZD0780 on the PK of midazolam (Part 3) and EE and LNG (Part 4).
Time frame: Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)
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* Period 1 (midazolam administration only). * Period 3 (AZD0780 + midazolam administration).
* Period 1 (EE and LNG administration only). * Period 3 (AZD0780 + EE and LNG administration).
CL/F (Apparent total body clearance)
To describe the PK of AZD0780 when administered alone, in combination with itraconazole or in combination with carbamazepine.
Time frame: Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)
t½λz (Terminal elimination half-life)
To describe the PK of AZD0780 when administered alone, in combination with itraconazole or in combination with carbamazepine.
Time frame: Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)
tmax (Time to reach maximum observed concentration)
To describe the PK of AZD0780 when administered alone, in combination with itraconazole or in combination with carbamazepine.
Time frame: Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)
Vz/F (Apparent volume of distribution based on the terminal phase)
To describe the PK of AZD0780 when administered alone, in combination with itraconazole or in combination with carbamazepine.
Time frame: Period 1 (Day 1 to 11 Cohort 1 and Cohort 2) and Period 3 (Day 14-24 Part 1 and Day 27-37 Part 2)
Number of participants with Adverse Events and Serious Adverse Events (AEs and SAEs)
To assess the safety and tolerability of AZD0780 when administered alone and in combination with itraconazole, carbamazepine, midazolam and EE and LNG.
Time frame: From Baseline until Follow-up Visit (7 to 14 days post-discharge)
Number of participants with treatment emergent abnormal ECGs
To assess the safety and tolerability of AZD0780 when administered alone and in combination with itraconazole, carbamazepine, midazolam and EE and LNG.
Time frame: From Baseline until Follow-up Visit (7 to 14 days post-discharge)
Vital signs and laboratory test results
To assess the safety and tolerability of AZD0780 when administered alone and in combination with itraconazole, carbamazepine, midazolam and EE and LNG.
Time frame: From Baseline until Follow-up Visit (7 to 14 days post-discharge)
CL/F
To describe the PK of midazolam (Part 3) and EE and LNG (Part 4) when administered alone and in combination with AZD0780.
Time frame: Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)
t½λz
To describe the PK of midazolam (Part 3) and EE and LNG (Part 4) when administered alone and in combination with AZD0780.
Time frame: Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)
tmax
TTo describe the PK of midazolam (Part 3) and EE and LNG (Part 4) when administered alone and in combination with AZD0780.
Time frame: Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)
Vz/F
To describe the PK of midazolam (Part 3) and EE and LNG (Part 4) when administered alone and in combination with AZD0780.
Time frame: Period 1 (Day 1 to 2 Part 3 and Day 1 to 7 Part 4) and Period 3 (Day 11-12 Part 3 and Day 16 to 22 Part 4)