Effect of capivasertib on how the body handles oral dextromethorphan in healthy adults

An Open-label, Fixed-sequence Study to Assess the Effect of Capivasertib on the Pharmacokinetics of Oral Dextromethorphan (CYP2D6 Substrate) in Healthy Participants.

This trial tests whether taking capivasertib changes how healthy adults absorb and break down a single oral dose of dextromethorphan.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 1 site (Berlin)
• Trial ID: NCT07241065 on ClinicalTrials.gov

What this trial studies

This open-label, fixed-sequence phase 1 trial at a single centre in Berlin examines the pharmacokinetic interaction between capivasertib and oral dextromethorphan in healthy participants. After screening, participants remain in-house from Day -1 to Day 8 and receive a single dose of dextromethorphan in Period 1 followed by capivasertib plus a single dose of dextromethorphan in Period 2. Blood (and possibly urine) samples are collected over time to measure drug and metabolite levels and determine changes in absorption, metabolism, and clearance. A follow-up visit is scheduled 7–10 days after the last dose to check safety and finalize sample collection.

Who should consider this trial

Good fit: Ideal candidates are healthy adult volunteers who meet the BMI and weight criteria, have no significant medical conditions, and agree to the contraception and in-house stay requirements.

Not a fit: People with any clinically important illness, gastrointestinal/hepatic/renal disease, pregnant or breastfeeding women, or those on interacting medications are unlikely to benefit and would be excluded.

Why it matters

Potential benefit: If successful, the results could help clinicians predict and manage drug interactions involving capivasertib and other medications metabolized by CYP2D6.

How similar studies have performed: Other drug–drug interaction studies with kinase inhibitors have shown effects on CYP enzymes in some cases, but the specific capivasertib–dextromethorphan interaction is novel and requires direct measurement.

Eligibility criteria

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

Where this trial is running

Berlin

• Research Site — Berlin, Germany (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

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