Pharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition

s63950

Short bowel syndrome (SBS) is defined as a loss of function of the small intestine resulting in a malabsorptive disorder. In SBS, oral drug absorption may be altered due to extensive intestinal resection. It remains unclear to what extent apixaban exposure is impacted in SBS.Therefore this study tries to investigate the pharmacokinetics (PK) of apixaban in adult patients with SBS requiring long-term parenteral nutrition (PN).

2020-12-20

2024-12-01

2024-12-01

Recruiting

Early phase I

84

Inclusion criteria SBS single dose: - patients with SBS (small bowel length of \<2m after Treitz ligament) on long term (\>3 months) PN or fluids who are apixaban-, vitamin K antagonist- and teduglutide naive Inclusion criteria SBS steady-state: - patients with SBS (small bowel length of \<2m after Treitz ligament) on long term (\>3 months) PN or fluids who are teduglutide naive and who are already taking apixaban 2,5 mg or 5 mg twice daily for ≥ 4 days Inclusion criteria non-SBS single dose: - healthy individuals without history of GI resections or other conditions associated with impaired absorption, who are apixaban- and vitamin K antagonist naive Inclusion criteria non-SBS steady-state: - patients without history of gastrointestinal resections or other conditions associated with impaired absorption (= controls), who are already taking apixaban 2,5 mg or 5 mg twice daily for ≥ 4 days Exclusion criteria SBS (single dose+ steady-state): * \<18 years * non-Dutch speaking * recent (\<6 months) major bleeds according with the International Society on Thrombosis and Haemostasis definition of major bleeding in non-surgical patients (20) * creatinine clearance of \< 15 mL/min or dialysis dependent * liver failure classified as Child Pugh C * total bilirubin ≥ 1.77 mg/dL (= 1,5 x upper limit of normal) * presence of coagulopathy and a clinically relevant bleeding risk * pregnancy or lactation * concomitant intake of strong combined inhibitors of CYP3A4 and P-gp * participation in a recent (\<1 month) trial with an investigational product * recent (\<6 months) gastrointestinal surgery * gastrointestinal mucosal disease interfering with absorption (e.g. radio-enteritis, inflammatory bowel disease, celiac disease, ...) * gastrointestinal fistulae * SBS with intestinal failure resulting from gastric bypass surgery Exclusion criteria non-SBS (single dose+ steady-state): * \<18 years * non-Dutch speaking * recent (\<6 months) major bleeds according with the International Society on Thrombosis and Haemostasis definition of major bleeding in non-surgical patients (20) * creatinine clearance of \< 15 mL/min or dialysis dependent * liver failure classified as Child Pugh C * total bilirubin ≥ 1.77 mg/dL (= 1,5 x upper limit of normal) * presence of coagulopathy and a clinically relevant bleeding risk * pregnancy or lactation * concomitant intake of strong combined inhibitors of CYP3A4 and P-gp * use of prokinetics, antimotility drugs or opioids * participation in a recent (\<1 month) trial with an investigational product

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Interventional, non-randomized, open label, monocentric controlled study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 84, 'type': 'ESTIMATED'}}

2024-02-23