Rivaroxaban Sotorasib Interaction Study

Conditions

• Drug Drug Interaction Study

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Accepted

Interventions

• Rivaroxaban 20mg — DRUG
  Single dose on day 1 and day 16
• Sotorasib 960mg — DRUG
  Daily dose from day 3 till day 16

Study Details

Venous thromboembolic Events (VTEs) are common in lung cancer patients with an incidence of \>15%, requiring anticoagulant treatment or prophylaxis. Although direct acting oral anticoagulants (DOACs) are the agents of first choice due to ease and patient friendliness, these drugs are often avoided in cancer patients due to suspected pharmacokinetic drug-drug interactions with oncolytic drugs. Sotorasib is the first KRASG12C inhibitor that has been approved by the US \[FDA\] and EU \[EMA\] for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC. Sotorasib has a potential to cause CYP3A-mediated drug-drug interactions due to induction of CYP3A and inhibition of P-GP. Rivaroxaban is the most frequently prescribed DOAC in the Netherlands. As rivaroxaban is a substrate for this enzyme and efflux pump, sotorasib may increase or decrease the exposure to rivaroxaban and, thus, impact its benefit-to-risk ratio. To enable safe combination of sotorasib and rivaroxaban, it is pivotal to investigate the magnitude of the pharmacokinetic interaction between these drugs.

Key Dates

Start date

Nov 9, 2023

Status verified

Jan 2024

Primary completion

Mar 21, 2024

Completion

Mar 21, 2024

Study Design

Enrollment

21 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Arms

• Experimental: Single dose rivaroxaban 20 mg and steady-state sotorasib 960 mg
  To assess the pharmacokinetics of single dose rivaroxaban in presence and absence of 960 mg sotorasib at pharmacokinetic steady-state. Samples will be taken pre-dose (t=0) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post ingestion.

Primary Outcome Measure

The pharmacokinetics (AUC) of single dose rivaroxaban in presence and absence of 960 mg sotorasib at pharmacokinetic steady-state. [ Time Frame: 18 days ]