A Study to Investigate the Effect of Capivasertib on the Pharmacokinetics of Oral Dextromethorphan (CYP2D6 Substrate) in Healthy Participants

Phase 1Not Yet RecruitingNCT07241065

AstraZeneca35 enrolled

Overview

The purpose of this study is to assess the effect of capivasertib on the pharmacokinetics of oral dextromethorphan in healthy participants.

This is an open-label, fixed sequence study conducted at a single study centre. The study will comprise of: * A Screening Period (from Day -28 to Day -2) * In-house treatment period (from Day -1 to Day 8) Period 1 (from Day -1 to Day 3): Participants will receive single oral doses of dextromethorphan during this period. Period 2 (from Day 4 to Day 8): Participants will receive 2 doses of capivasertib and a single dose of dextromethorphan during this period. • Follow-up Visit within 7 to 10 days after the last administration of the Investigative Medical Products (from Day 13 to Day 16).

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy Participants

Interventions

DextromethorphanDRUG

Dextromethorphan will be administered orally once in Period 1 and once in Period 2

CapivasertibDRUG

Capivasertib will be administered orally twice in Period 2

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Main Inclusion Criteria: * Have a Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg. * All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit. * Females of non-childbearing potential must be confirmed at the screening visit (postmenopausal or documentation of irreversible surgical sterilisation). * Male participants must have documentation of vasectomy done 6 months prior to screening visit. Participants must be willing to use one barrier method of contraception (condom) during sexual intercourse with a female partner of childbearing potential from the time of first study intervention administration until 16 weeks after the last dose of capivasertib. Main Exclusion Criteria: * History of any clinically important disease or disorder * History or presence of gastrointestinal, hepatic or renal disease. * Any clinically important illness, medical/surgical procedure (excluding placement of vascular access), or significant traumatic injury within 4 weeks of the first administration of study intervention or an anticipated need for major surgery during the study. * Any clinically significant skin abnormalities that are chronic or currently active. * Abnormal hepato-renal and bone marrow organ function laboratory values. * Any clinically important abnormalities in clinical chemistry, haematology, or urinalysis. * Any clinically significant abnormalities in glucose metabolism. * Any positive result on screening for serum HBsAg OR anti-HBc antibody, indicative of active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) * Current smokers or those who have smoked or used other nicotine/nicotine-containing products within the previous 3 months prior to Screening Visit. * Known or suspected history of alcohol or drug abuse or excessive intake of alcohol. * Use of drugs with enzyme inducing properties 3 weeks prior to the first administration of study intervention. * Use of strong inhibitors of Cytochrome P450 3A4 (CYP3A4) or strong/moderate inducers of CYP3A4 within 2 weeks prior to first dose of capivasertib. * Concurrent use of herbal or natural products intended as treatment or prophylaxis that may interact with capivasertib. * Participants who have previously received capivasertib. * Any clinically significant abnormal findings in vital signs and 12-lead electrocardiogram (ECG). * History of severe allergy/hypersensitivity

Outcomes

Primary Outcomes

Area under concentration time curve from time 0 to infinity (AUCinf) of dextromethorphan

To evaluate the PK (AUCinf) of dextromethorphan when administered orally alone and following oral dosing of capivasertib

Time frame: Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8

Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) of dextromethorphan

To evaluate the PK (AUClast) of dextromethorphan when administered orally alone and following oral dosing of capivasertib

Time frame: Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8

Maximum observed drug concentration (Cmax) of dextromethorphan

To evaluate the PK (Cmax) of dextromethorphan when administered orally alone and following oral dosing of capivasertib

Time frame: Period 1: Day 1 to Day 3, Period 2: Day 6 to Day 8

Secondary Outcomes

Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) of capivasertib

To evaluate the PK (AUClast) of capivasertib following oral dosing

Time frame: Period 2: Day 5 to Day 8

Time to reach maximum observed concentration (tmax) of capivasertib

To evaluate the PK (tmax) of capivasertib following oral dosing

Time frame: Period 2: Day 5 to Day 8

Maximum observed drug concentration (Cmax) of capivasertib

To evaluate the PK (Cmax) of capivasertib following oral dosing

Time frame: Period 2: Day 5 to Day 8

Ratio of AUCinf following co-administration to AUCinf following dosing alone (R AUCinf) of dextromethorphan

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

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