Rivaroxaban sotorasib interaction study

Phase 1

• Conditions: Healthy subjects; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; Therapeutic area: Phenomena and Processes [G] - Metabolism [G03]

• Registration Number: CTIS2023-505557-41-00
• Lead Sponsor: Stichting Radboud University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-05-17
• Study Completion: 2024-03-21
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Subject is at least 18 and not older than 65 years at screening., Subject does not smoke more than 10 (e-)cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first study day., Subject has a Body Mass Index of 18 to 30 kg/m2 ., Subject is able and willing to sign the Informed Consent Form prior to screening evaluations., Subject is in good age-appropriate health condition as established by medical history and physical examination within 4 weeks prior to day 1., Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.

Exclusion Criteria

An estimated glomerular filtration or creatinine clearance of less than 70mL/min., Female subjects of childbearing potential unwilling to use an effective method of contraception during treatment and for an additional 7 days after the last dose of sotorasib., Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 7 days after the last dose of sotorasib., Male subjects unwilling to abstain from donating sperm during treatment and for an additional 7 days after the last dose of sotorasib., Consumption of foods and beverages containing poppy seeds, St. Johns Wort, grapefruit, or Seville oranges within 7 days prior to check-in., Concomitant use of drugs, including herbs and food additives, with a pharmacokinetic or pharmacodynamic interaction, as assessed with most recent KNMP kennisbank and uptodate.com drug interaction databases., Donation of plasma or blood (450ml or more) less than 2 months before start of the study., Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion., History of or current abuse of drugs or alcohol., Inability to understand the nature and extent of the study and the procedures required., Febrile illness within 3 days before Day 1., Liver enzyme tests (ALAT, ASAT, GGT, total bilirubin, ALP) greater than 2 times the upper limit of normal., History of internal bleeding of any genesis., Known present congenital or acquired bleeding disorders., History of liver disease., History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, or duodenal ulceration or bowel disease (including but not limited to peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn’s disease, or irritable bowel syndrome); or a history of gastrointestinal surgery other than uncomplicated appendectomy., Known gastrointestinal disease without active ulceration that can potentially lead to bleeding complications., History of vascular retinopathy., Known bronchiectasis., History of pulmonary bleeding., The following conditions known in medical history: coronary heart disease, previous cerebrovascular accident (CVA) or transient ischaemic attack., Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B or recent acute hepatitis B). Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B core antibody testing is not required for screening, however if this is done and is positive, then hepatitis B surface antibody [anti-HBs] testing is necessary. Undetectable anti-HBs in this setting would suggest unclear and possible infection and needs exclusion)., Serum electrolytes (sodium, potassium, calcium, magnesium) outside the normal range of the NVKC reference ranges., Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction (PCR) is necessary. Detectable Hepatitis C virus RNA suggests chronic hepatitis C., Hemocytometric values (hemoglobin, hematocrit, leukocytes, erythrocytes and thrombocytes) outside of the NVKC reference ranges., A prothrombin time (PT) > 13.3 seconds., An activated partial thromboplastin time (APTT) >38 seconds., Clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood.,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the pharmacokinetics of single dose rivaroxaban in presence and absence of 960 mg sotorasib at pharmacokinetic steady-state.;Secondary Objective: To assess the pharmacokinetics of sotorasib in healthy volunteers., To evaluate the safety of sotorasib and rivaroxaban.;Primary end point(s): The geometric mean ratios of AUC and Cmax of rivaroxaban in absence and presence of sotorasib.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Description of the pharmacokinetics of sotorasib in healthy volunteers, by means of standard compartmental or non-compartmental pharmacokinetic methods.;Secondary end point(s):Description of the safety of sotorasib and rivaroxaban, graded with the most recent version (v6) of the Common Toxicity Criteria for Adverse Events.