Back to resultsPharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition (ABSORB)
Primary Purpose
Short Bowel Syndrome, Anticoagulation
Status
Recruiting
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Apixaban single dose
Apixaban steady-state
Sponsored by
About this trial
This is an interventional treatment trial for Short Bowel Syndrome focused on measuring Apixaban, Pharmacokinetics
Eligibility Criteria
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 anticoagulation 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 anticoagulation 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 other anticoagulant agents
- 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 other anticoagulant agents
- 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
Sites / Locations
- University Hospitals LeuvenRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Other
Other
Experimental
Arm Label
Anticoagulation and teduglutide naive short bowel syndrome
Healthy volunteers
Short bowel syndrome on apixaban
Patients with a normal gastrointestinal tract on apixaban
Anticoagulation naive short bowel syndrome on teduglutide
Arm Description
Anticoagulation and teduglutide naive patients with short bowel syndrome requiring long term parenteral support
Anticoagulation naive healty volunteers
Patients with short bowel syndrome requiring long term parenteral support and taking apixaban 2.5 mg twice daily or 5 mg twice daily
Patients with a normal gastrointestinal tract taking apixaban 2.5 mg twice daily or 5 mg twice daily
Anticoagulation naive patients with short bowel syndrome requiring long term parenteral support and initiated on teduglutide
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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
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
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
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
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
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.
Difference in Cmax between SBS patients with and without teduglutide
To investigate the difference in Cmax between SBS patients with and without teduglutide
Difference in Cmin between SBS patients with and without teduglutide
To investigate the difference in Cmin between SBS patients with and without teduglutide
Difference in Tmax between SBS patients with and without teduglutide
To investigate the difference in Tmax between SBS patients with and without teduglutide
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
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
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
Difference in bioavailability between SBS patients with and without teduglutide
To investigate the difference in bioavailability between SBS patients with and without teduglutide
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
Difference in clearance between SBS patients with and without teduglutide
To investigate the difference in clearance between SBS patients with and without teduglutide
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
Full Information
NCT ID
NCT04344717
First Posted
April 3, 2020
Last Updated
August 25, 2022
Sponsor
Universitaire Ziekenhuizen KU Leuven
1. Study Identification
Unique Protocol Identification Number
NCT04344717
Brief Title
Pharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition
Acronym
ABSORB
Official Title
Pharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 20, 2020 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Short Bowel Syndrome, Anticoagulation
Keywords
Apixaban, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Interventional, non-randomized, open label, monocentric controlled study
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anticoagulation and teduglutide naive short bowel syndrome
Arm Type
Experimental
Arm Description
Anticoagulation and teduglutide naive patients with short bowel syndrome requiring long term parenteral support
Arm Title
Healthy volunteers
Arm Type
Experimental
Arm Description
Anticoagulation naive healty volunteers
Arm Title
Short bowel syndrome on apixaban
Arm Type
Other
Arm Description
Patients with short bowel syndrome requiring long term parenteral support and taking apixaban 2.5 mg twice daily or 5 mg twice daily
Arm Title
Patients with a normal gastrointestinal tract on apixaban
Arm Type
Other
Arm Description
Patients with a normal gastrointestinal tract taking apixaban 2.5 mg twice daily or 5 mg twice daily
Arm Title
Anticoagulation naive short bowel syndrome on teduglutide
Arm Type
Experimental
Arm Description
Anticoagulation naive patients with short bowel syndrome requiring long term parenteral support and initiated on teduglutide
Intervention Type
Drug
Intervention Name(s)
Apixaban single dose
Other Intervention Name(s)
Eliquis single dose
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Apixaban steady-state
Other Intervention Name(s)
Eliquis steady-state
Intervention Description
Steady-state apixaban PK characteristics will be measured in patients already treated with apixaban
Primary Outcome Measure Information:
Title
Difference in Cmax of apixaban between SBS and patients with a normal gastrointestinal tract
Description
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 Outcome Measure Information:
Title
Difference in estimated trough level (Cmin) of apixaban between SBS and patients with a normal gastrointestinal tract
Description
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
Title
Difference in time to reach Cmax (Tmax) of apixaban between SBS patients and patients with a normal gastrointestinal tract
Description
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
Title
Difference in exposure (AUC0-12h) of apixaban between SBS patients and patients with a normal gastrointestinal tract
Description
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
Title
Difference in absorption rate constant of apixaban between SBS patients and patients with a normal gastrointestinal tract
Description
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
Title
Difference in bioavailability of apixaban between SBS patients and patients with a normal gastrointestinal tract
Description
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
Title
Difference in volume of distribution of apixaban between SBS patients and patients with a normal gastrointestinal tract
Description
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
Title
Difference in clearance of apixaban between SBS patients and patients with a normal gastrointestinal tract
Description
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
Title
Difference in half-life of apixaban between SBS patients and patients with a normal gastrointestinal tract
Description
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
Title
To set up an optimized dosing scheme of apixaban for SBS patients
Description
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
Title
Difference in Cmax between SBS patients with and without teduglutide
Description
To investigate the difference in Cmax between SBS patients with and without teduglutide
Time Frame
Through study completion, an average of 1.5 years
Title
Difference in Cmin between SBS patients with and without teduglutide
Description
To investigate the difference in Cmin between SBS patients with and without teduglutide
Time Frame
Through study completion, an average of 1.5 years
Title
Difference in Tmax between SBS patients with and without teduglutide
Description
To investigate the difference in Tmax between SBS patients with and without teduglutide
Time Frame
Through study completion, an average of 1.5 years
Title
Difference in AUC SBS patients with and without teduglutide
Description
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
Title
Difference in AUC between SBS patients with and without teduglutide
Description
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
Title
Difference in absorption rate constant between SBS patients with and without teduglutide
Description
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
Title
Difference in bioavailability between SBS patients with and without teduglutide
Description
To investigate the difference in bioavailability between SBS patients with and without teduglutide
Time Frame
Through study completion, an average of 1.5 years
Title
Difference in volume of distribution between SBS patients with and without teduglutide
Description
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
Title
Difference in clearance between SBS patients with and without teduglutide
Description
To investigate the difference in clearance between SBS patients with and without teduglutide
Time Frame
Through study completion, an average of 1.5 years
Title
Difference in half-life between SBS patients with and without teduglutide
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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 anticoagulation 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 anticoagulation 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 other anticoagulant agents
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 other anticoagulant agents
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara Deleenheer, PharmD
Phone
003216342504
Email
barbara.deleenheer@uzleuven.be
Facility Information:
Facility Name
University Hospitals Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barbara Deleenheer, PharmD
Email
barbara.deleenheer@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Deleenheer
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Individual participant data will be coded according to General Data Protection Regulation
Citations:
PubMed Identifier
24486858
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.
Results Reference
background
PubMed Identifier
30136101
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.
Results Reference
background
PubMed Identifier
28355459
Citation
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.
Results Reference
background
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Pharmacokinetics of Apixaban in Patients With Short Bowel Syndrome Requiring Long Term Parenteral Nutrition
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