A Study to Investigate the Pharmacokinetics of Midazolam After Repeated Doses of Camizestrant (AZD9833) and to Investigate the Pharmacokinetics of Camizestrant When Administered Alone and in Combination With Carbamazepine in Healthy Post-Menopausal Female Participants
NCT Number: NCT06547164
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Healthy Participants
Interventions: DRUG: Midazolam|DRUG: Camizestrant|DRUG: Carbamazepine
Sponsor: AstraZeneca
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-27
Completion Date: 2025-03-05
Locations: Research Site, Harrow, HA1 3UJ, United Kingdom

Summary:
This study will be conducted in order to determine the effect of repeated oral doses of camizestrant on the pharmacokinetics (PK) of midazolam and to determine the effect of repeated oral titrated doses of carbamazepine on the PK of camizestrant in healthy post-menopausal female participants.

Primary Outcome Measures: Part A: Area under concentration-time curve from time 0 to infinity (AUCinf) of midazolam, To determine the effect of repeated oral doses of camizestrant on the key PK parameters of a single oral dose of midazolam in healthy postmenopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part A: Area under concentrationcurve from time 0 to the last quantifiable concentration (AUClast) of midazolam, To determine the effect of repeated oral doses of camizestrant on the key PK parameters of a single oral dose of midazolam in healthy postmenopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part A: Maximum observed plasma (peak) drug concentration (Cmax) of midazolam, To determine the effect of repeated oral doses of camizestrant on the key PK parameters of a single oral dose of midazolam in healthy postmenopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part B: Area under concentration-time curve from time 0 to infinity (AUCinf) of camizestrant, To determine the effect of repeated oral titrated doses of carbamazepine on the PK of a single oral dose of camizestrant in healthy postmenopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)|Part B: Area under concentrationcurve from time 0 to the last quantifiable concentration (AUClast) of camizestrant, To determine the effect of repeated oral titrated doses of carbamazepine on the PK of a single oral dose of camizestrant in healthy postmenopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)|Part B: Maximum observed plasma (peak) drug concentration (Cmax) of camizestrant, To determine the effect of repeated oral titrated doses of carbamazepine on the PK of a single oral dose of camizestrant in healthy postmenopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)
Secondary Outcome Measures: Part A: Time to reach maximum observed concentration (tmax) of midazolam, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part A: Terminal elimination half-life (t½λz) of midazolam, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part A: Terminal rate constant (λz) of midazolam, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part A: Apparent total body clearance (CL/F) of midazolam, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part A: Apparent volume of distribution based on the terminal phase (Vz/F) of midazolam, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1) and Period 3 (Day 7 to Day 8)|Part A: Plasma concentration of camizestrant, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 3: Pre-dose and 3 hours post-dose of Day 7 and Day 8|Part B: Time to reach maximum observed concentration (tmax) of camizestrant, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)|Part B: Terminal elimination half-life (t½λz) of camizestrant, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)|Part B: Terminal rate constant (λz) of camizestrant, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)|Part B: Apparent total body clearance (CL/F) of camizestrant, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)|Part B: Apparent volume of distribution based on the terminal phase (Vz/F) of camizestrant, To further characterise the effect of camizestrant on the PK of midazolam, and the effect of carbamazepine on the PK of camizestrant, in healthy post-menopausal female participants., Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)|Number of participants with adverse events (AEs) and serious adverse events (SAEs), To evaluate the safety and tolerability of camizestrant, alone and in combination with midazolam and carbamazepine, respectively, in healthy post-menopausal female participants., For SAEs - Part A: From screening (Day -28 to Day -2) to 7 weeks; Part B: From screening (Day -28 to Day -2) to 9 weeks. For AEs: Part A: From Day 1 to 7 weeks; Part B: From Day 1 to 9 weeks