Rivaroxaban sotorasib interaction study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud University Medical Center

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Phenomena and Processes [G] - Metabolism [G03]

Trial duration

9 Nov 2023 → 21 Mar 2024

Decision date (initial)

2023-08-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AMGEN

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

To assess the pharmacokinetics of single dose rivaroxaban in presence and absence of 960 mg sotorasib at pharmacokinetic steady-state.

Secondary objectives 2

1. To assess the pharmacokinetics of sotorasib in healthy volunteers.
2. To evaluate the safety of sotorasib and rivaroxaban.

Conditions and MedDRA coding

Healthy subjects

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subject is at least 18 and not older than 65 years at screening.
2. 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.
3. Subject has a Body Mass Index of 18 to 30 kg/m2 .
4. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
5. Subject is in good age-appropriate health condition as established by medical history and physical examination within 4 weeks prior to day 1.
6. Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.

Exclusion criteria 30

1. An estimated glomerular filtration or creatinine clearance of less than 70mL/min.
2. Liver enzyme tests (ALAT, ASAT, GGT, total bilirubin, ALP) greater than 2 times the upper limit of normal.
3. Serum electrolytes (sodium, potassium, calcium, magnesium) outside the normal range of the NVKC reference ranges.
4. Hemocytometric values (hemoglobin, hematocrit, leukocytes, erythrocytes and thrombocytes) outside of the NVKC reference ranges.
5. A prothrombin time (PT) > 13.3 seconds.
6. An activated partial thromboplastin time (APTT) >38 seconds.
7. Clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood.
8. Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
9. Female subject is pregnant or lactating/breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 7 days after the last dose of sotorasib.
10. 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.
11. 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.
12. Male subjects unwilling to abstain from donating sperm during treatment and for an additional 7 days after the last dose of sotorasib.
13. Consumption of foods and beverages containing poppy seeds, St. Johns Wort, grapefruit, or Seville oranges within 7 days prior to check-in.
14. 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.
15. Donation of plasma or blood (450ml or more) less than 2 months before start of the study.
16. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
17. History of or current abuse of drugs or alcohol.
18. Inability to understand the nature and extent of the study and the procedures required.
19. Febrile illness within 3 days before Day 1.
20. History of internal bleeding of any genesis.
21. Known present congenital or acquired bleeding disorders.
22. History of liver disease.
23. 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.
24. Known gastrointestinal disease without active ulceration that can potentially lead to bleeding complications.
25. History of vascular retinopathy.
26. Known bronchiectasis.
27. History of pulmonary bleeding.
28. The following conditions known in medical history: coronary heart disease, previous cerebrovascular accident (CVA) or transient ischaemic attack.
29. 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).
30. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The geometric mean ratios of AUC and Cmax of rivaroxaban in absence and presence of sotorasib.

Secondary endpoints 2

1. Description of the pharmacokinetics of sotorasib in healthy volunteers, by means of standard compartmental or non-compartmental pharmacokinetic methods.
2. Description of the safety of sotorasib and rivaroxaban, graded with the most recent version (v6) of the Common Toxicity Criteria for Adverse Events.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud University Medical Center

Sponsor organisation

Stichting Radboud University Medical Center

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Investigator

Public contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications