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.
This is an open-label, fixed sequence, 2-part (Part A and Part B), drug-drug interaction study in healthy post-menopausal female participants. Participants enrolled in Part A may subsequently also participate in Part B. Part A of the study will assess the effect of repeated oral doses of camizestrant on the PK of a single oral dose of midazolam. It will comprise: * A Screening Period of maximum 28 days. * Three Treatment Periods during which participants will be resident at the Clinical Unit from the day before study intervention administration (Day -1) until after the last camizestrant PK sample on Day 8. 1. Period 1: participants will receive a single oral dose of midazolam (Day 1). 2. Period 2: participants will receive an oral once daily (OD) dose of camizestrant (Day 2 to Day 6). 3. Period 3: participants will receive a single oral dose of midazolam and camizestrant (Day 7). * A Follow-up Visit, for which the participant will return to the Clinical Unit 7 (± 2) days after the last camizestrant PK sample in Period 3. Part B of the study will assess the effect of multiple oral doses of carbamazepine on the PK of a single oral dose of camizestrant. It will comprise: * A Screening Period of maximum 28 days. * Two Treatment Periods during which participants will be resident at the Clinical Unit from the day before study intervention administration (Day -1) until after the last camizestrant PK sample on Day 16. 1. Period 1: participants will receive a single oral dose of camizestrant (Day 1) with PK sampling on Day 1 to Day 4. 2. Period 2: participants will receive low oral doses (Dose 1) of carbamazepine twice a day (BID) on Day 4 to Day 6, mid oral doses (Dose 2) of carbamazepine BID on Day 7 to Day 9, and high oral doses (Dose 3) of carbamazepine BID on Day 10 to Day 15. On Day 13, participants will receive a single oral dose of camizestrant. * A Follow-up Visit, for which the participant will return to the Clinical Unit 7 (± 2) days after the last camizestrant PK sample in Period 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Midazolam will be administered orally.
Camizestrant will be administered orally.
Carbamazepine will be administered orally.
Research Site
Harrow, United Kingdom
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Period 1 (Day 1 to Day 4), Period 2 (Day 22 to Day 25)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Period 3: Pre-dose and 3 hours post-dose of Day 7 and Day 8
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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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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