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

NCT04344717 | Unknown Phase 4

• 1 other identifier: s63950
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Short Bowel Syndrome; Anticoagulation

Keywords

Apixaban; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (19)

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

  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

  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

  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

  Through study completion, an average of 1.5 years

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

  Through study completion, an average of 1.5 years

Study Arms (5)

Anticoagulation and teduglutide naive short bowel syndrome

EXPERIMENTAL

Apixaban-, vitamin K antagonist- and teduglutide naive patients with short bowel syndrome requiring long term parenteral support

Drug: Apixaban single dose

Healthy volunteers

EXPERIMENTAL

Apixaban- and vitamin K antagonist naive healty volunteers

Drug: Apixaban single dose

Short bowel syndrome on apixaban

OTHER

Patients with short bowel syndrome requiring long term parenteral support and taking apixaban 2.5 mg twice daily or 5 mg twice daily

Drug: Apixaban steady-state

Patients with a normal gastrointestinal tract on apixaban

OTHER

Patients with a normal gastrointestinal tract taking apixaban 2.5 mg twice daily or 5 mg twice daily

Drug: Apixaban steady-state

Anticoagulation naive short bowel syndrome on teduglutide

EXPERIMENTAL

Apixaban- and vitamin K antagonist naive patients with short bowel syndrome requiring long term parenteral support and initiated on teduglutide

Drug: Apixaban single dose

Interventions

Apixaban single dose DRUG

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

Also known as: Eliquis single dose

Anticoagulation and teduglutide naive short bowel syndrome; Anticoagulation naive short bowel syndrome on teduglutide; Healthy volunteers

Apixaban steady-state DRUG

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

Also known as: Eliquis steady-state

Patients with a normal gastrointestinal tract on apixaban; Short bowel syndrome on apixaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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
• \- 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
• \- healthy individuals without history of GI resections or other conditions associated with impaired absorption, who are apixaban- and vitamin K antagonist naive
• \- 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

You may not qualify if:

• \<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
• \<18 years

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, 3000, Belgium

RECRUITING

Related Publications (3)

• 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.

  PMID: 24486858 BACKGROUND

• 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.

  PMID: 30136101 BACKGROUND

• 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.

  PMID: 28355459 BACKGROUND

MeSH Terms

Conditions

Short Bowel Syndrome

Interventions

apixaban

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Barbara Deleenheer, PharmD

CONTACT

003216342504; barbara.deleenheer@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional, non-randomized, open label, monocentric controlled study

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 14, 2020
• Study Start: December 20, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 23, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)