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

NCT07241065 | Recruiting Phase 1

• 1 other identifier: D3615C00005
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Participants

Keywords

Serine/protein kinase AKT; Anti-cancer agent; Pharmacokinetics; Protein kinase

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

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

Secondary Outcomes (18)

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

  Period 2: Day 5 to Day 8

• Time to reach maximum observed concentration (tmax) of capivasertib

  Period 2: Day 5 to Day 8

• Maximum observed drug concentration (Cmax) of capivasertib

  Period 2: Day 5 to Day 8

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

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

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

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

Study Arms (1)

Dextromethorphan/ Dextromethorphan + Capivasertib

EXPERIMENTAL

Participants will receive a single dose of dextromethorphan in Period 1. After a minimum washout period of 4 days from the first dose of dextromethorphan, participants will receive the first dose of capivasertib, followed by a second dose of capivasertib after 12 hours, administered concomitantly with a single dose of dextromethorphan in Period 2.

Drug: Dextromethorphan; Drug: Capivasertib

Interventions

Dextromethorphan DRUG

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

Dextromethorphan/ Dextromethorphan + Capivasertib

Capivasertib DRUG

Capivasertib will be administered orally twice in Period 2

Dextromethorphan/ Dextromethorphan + Capivasertib

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

RECRUITING

Related Links

• Thank You Card English
• Thank You Card German

MeSH Terms

Interventions

Dextromethorphan; capivasertib

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 21, 2025
• Study Start: March 19, 2026
• Primary Completion (Estimated): June 17, 2026
• Study Completion (Estimated): June 17, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

DE (1)