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

Short Bowel Syndrome Clinical Trial

— ABSORB  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04344717
• Other study ID #: s63950
• Status: Recruiting
• Phase: Phase 4
• Start date: December 20, 2020
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Barbara Deleenheer, PharmD
• Phone: 003216342504
• Email: barbara.deleenheer[@]uzleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anticoagulation
• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• Apixaban single dose
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-state
Steady-state apixaban PK characteristics will be measured in patients already treated with apixaban

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (3)

Eikelboom JW, Quinlan DJ, Hirsh J, Connolly SJ, Weitz JI. Laboratory Monitoring of Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation: A Review. JAMA Cardiol. 2017 May 1;2(5):566-574. doi: 10.1001/jamacardio.2017.0364. — View Citation

Jeppesen PB. Spectrum of short bowel syndrome in adults: intestinal insufficiency to intestinal failure. JPEN J Parenter Enteral Nutr. 2014 May;38(1 Suppl):8S-13S. doi: 10.1177/0148607114520994. Epub 2014 Jan 31. — View Citation

Santamaria MM, Villafranca JJA, Abiles J, Lopez AF, Rodas LV, Goitia BT, Navarro PU. Systematic review of drug bioavailability following gastrointestinal surgery. Eur J Clin Pharmacol. 2018 Dec;74(12):1531-1545. doi: 10.1007/s00228-018-2539-9. Epub 2018 Aug 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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.	Through study completion, an average of 1.5 years
Secondary	Difference in Cmax between SBS patients with and without teduglutide	To investigate the difference in Cmax between SBS patients with and without teduglutide	Through study completion, an average of 1.5 years
Secondary	Difference in Cmin between SBS patients with and without teduglutide	To investigate the difference in Cmin between SBS patients with and without teduglutide	Through study completion, an average of 1.5 years
Secondary	Difference in Tmax between SBS patients with and without teduglutide	To investigate the difference in Tmax between SBS patients with and without teduglutide	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	Difference in bioavailability between SBS patients with and without teduglutide	To investigate the difference in bioavailability between SBS patients with and without teduglutide	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years
Secondary	Difference in clearance between SBS patients with and without teduglutide	To investigate the difference in clearance between SBS patients with and without teduglutide	Through study completion, an average of 1.5 years
Secondary	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	Through study completion, an average of 1.5 years