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

Universitaire Ziekenhuizen KU Leuven84 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Short Bowel Syndrome Anticoagulation

Interventions

Apixaban single doseDRUG

A single dose of apixaban 2.5 mg and 5 mg (wash out period of at least 7 days) will be administered and PK characteristics will be measured

Apixaban steady-stateDRUG

Steady-state apixaban PK characteristics will be measured in patients already treated with apixaban

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

University Hospitals Leuven

Leuven, Belgium

RECRUITING

Outcomes

Primary Outcomes

Difference in Cmax of apixaban between SBS and patients with a normal gastrointestinal tract

To investigate the difference in peak level (Cmax) after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Secondary Outcomes

Difference in estimated trough level (Cmin) of apixaban between SBS and patients with a normal gastrointestinal tract

To investigate differences in estimated Cmin (12h after administration) after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Difference in time to reach Cmax (Tmax) of apixaban between SBS patients and patients with a normal gastrointestinal tract

To investigate differences in Tmax after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Difference in exposure (AUC0-12h) of apixaban between SBS patients and patients with a normal gastrointestinal tract

To investigate differences in AUC0-12 after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Difference in absorption rate constant of apixaban between SBS patients and patients with a normal gastrointestinal tract

To investigate the difference in absorption rate constant between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Central Contacts

Barbara Deleenheer, PharmD

CONTACT

003216342504 barbara.deleenheer@uzleuven.be

Data from ClinicalTrials.gov

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Difference in bioavailability of apixaban between SBS patients and patients with a normal gastrointestinal tract

To investigate the difference in bioavailability between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Difference in volume of distribution of apixaban between SBS patients and patients with a normal gastrointestinal tract

To investigate the difference in volume of distribution between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Difference in clearance of apixaban between SBS patients and patients with a normal gastrointestinal tract

To investigate the difference in clearance between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

Difference in half-life of apixaban between SBS patients and patients with a normal gastrointestinal tract

To investigate the difference in half-life between patients with and without SBS requiring long-term PN

Time frame: Through study completion, an average of 1.5 years

To set up an optimized dosing scheme of apixaban for SBS patients

To set up an optimized dosing scheme of apixaban, using PK modeling, for SBS patients taking into account identified covariates (eg. sex, age, race...) and PK measurements from outcome 1-9.

Time frame: Through study completion, an average of 1.5 years

Difference in Cmax between SBS patients with and without teduglutide

To investigate the difference in Cmax between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in Cmin between SBS patients with and without teduglutide

To investigate the difference in Cmin between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in Tmax between SBS patients with and without teduglutide

To investigate the difference in Tmax between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in AUC SBS patients with and without teduglutide

To investigate the difference in Cmax, Cmin, Tmax, AUC, absorption rate constant, bioavailability, volume of distribution, clearance and half-life between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in AUC between SBS patients with and without teduglutide

To investigate the difference in Cmax, Cmin, Tmax, AUC, absorption rate constant, bioavailability, volume of distribution, clearance and half-life between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in absorption rate constant between SBS patients with and without teduglutide

To investigate the difference in absorption rate constant between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in bioavailability between SBS patients with and without teduglutide

To investigate the difference in bioavailability between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in volume of distribution between SBS patients with and without teduglutide

To investigate the difference in volume of distribution between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in clearance between SBS patients with and without teduglutide

To investigate the difference in clearance between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years

Difference in half-life between SBS patients with and without teduglutide

To investigate the difference in half-life between SBS patients with and without teduglutide

Time frame: Through study completion, an average of 1.5 years