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Pharmacokinetics of Apixaban in Patients Undergoing Pancreaticoduodenectomy (PAP-UP)

Primary Purpose

Pancreas Cancer, DVT, Pulmonary Embolism

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Apixaban
Sponsored by
Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreas Cancer focused on measuring apixaban, pancreaticoduodenectomy, whipple, pharmacokinetic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Be a male or female between ages 18-65 (inclusive) at the screening visit
  • May have a history of pharmacologically well-controlled hypertension or non-insulin dependent diabetes
  • Have a body mass index (BMI) ≥ 19 and ≤ 33 (inclusive)
  • BMI = (weight (kg))/(height (m2))
  • Have a history of pancreaticoduodenectomy
  • If female, subject can be of childbearing potential and must demonstrate a urine β-hCG level consistent with the non-gravid state at the screening visit and agree to use (and/or have their partner use) an acceptable method of birth control beginning at the screening visit throughout the trial (including washout intervals between treatment periods) and until 2 weeks after the last dose of trial drug in the last treatment period. Acceptable methods of birth control: intrauterine device ("IUD" with or without local hormone release, oral contraceptive pills, diaphragm, cervical cap, spermicides, contraceptive sponge, and /or condoms). Abstinence is an alternative life style and subjects practicing abstinence may be included in the trial.
  • Can be of non-childbearing potential which is defined as: a female who is postmenopausal without menses for at least 1 year and an FSH value in the postmenopausal range upon screening evaluation and/or a female who is status post hysterectomy, oophorectomy or tubal ligation.
  • Have serum creatinine level < 1.5 mg/dL
  • Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal
  • Have platelet count within normal limits
  • Be willing to refrain from the use of anticoagulants and antiplatelet medications including aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) during the entire period of study participation
  • Be willing to comply with trial restrictions

Exclusion Criteria:

The subject will be excluded from participating in the trial if the subject:

  • Has a history of clinically significant medical condition that based upon the judgment of the investigator makes participation inappropriate
  • Has a history of a major bleeding event (defined as: (i) symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or (ii) a fall in hemoglobin level of 2 g/dL or more, or leading to transfusion of two or more units of whole blood or red cells) within 6 months prior to screening visit
  • Has had major surgery within 6 months prior to screening visit
  • Is actively taking any the following list of medications/supplements and cannot hold these medications for <5 half-lives prior to the study:
  • CYP3A4 Moderate/Strong Inhibitors:

Selective Serotonin Reuptake Inhibitors (SSRI) Amiodarone, Dronedarone Diltiazem Cimetidine Aprepitant Protease Inhibitors CYP3A4 Inducers Rifampin Phenytoin Carbemazepine Ritonavir St. John's Wort Enzalutamide Efavirenz Teriflunomide Bosentan Modafinil Mitotane Other Pancreatic Enzyme Replacement (Creon, Pancrelipase, Viokase)

  • Has a history of illicit drug abuse within six months prior to screening visit
  • Is an active smoker (last exposure <2 weeks prior to study screening)
  • Pregnant or lactating
  • Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day and cannot refrain from alcohol for the duration of the trial
  • Has a history of significant multiple and/or severe allergies (e.g. food, drug), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  • Has known anaphylactic or severe systemic reactions to any components of apixaban or contraindication to the administration of apixaban
  • Has moderate or severe hepatic disease or other clinically relevant bleeding risk
  • Use of any drugs or products which at the discretion of the investigator would increase bleeding risk
  • Is considered inappropriate for participation by the investigator for any reason

Sites / Locations

  • Thomas Jefferson University Clinical Research Unit

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Apixaban dosing

Arm Description

Subjects to receive single dose of apixaban

Outcomes

Primary Outcome Measures

Serum Apixaban Level
Serum apixaban PK level

Secondary Outcome Measures

Full Information

First Posted
December 6, 2019
Last Updated
December 6, 2021
Sponsor
Thomas Jefferson University
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1. Study Identification

Unique Protocol Identification Number
NCT04191928
Brief Title
Pharmacokinetics of Apixaban in Patients Undergoing Pancreaticoduodenectomy
Acronym
PAP-UP
Official Title
An Exploratory Study of the Pharmacokinetics of Apixaban in Patients Undergoing Pancreaticoduodenectomy
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
March 3, 2020 (Actual)
Primary Completion Date
July 25, 2020 (Actual)
Study Completion Date
September 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thomas Jefferson University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Study investigators will examine the absorption characteristics of apixaban, a direct-acting oral anticoagulation, in patients who have underwent a particular kind of surgery (pancreaticoduodenectomy) which involves resection of the duodenum.
Detailed Description
This study will examine apixaban pharmacokinetic exposure (AUC(0-24)) and maximum concentration (Cmax) when administered as a single oral dose in patients who have undergone pancreaticoduodenectomy (PD) compared to historical controls. This is a phase one, single dose pharmacokinetic study in stable patients who have undergone pancreaticoduodenectomy. Apixaban is an orally administered highly selective factor Xa inhibitor, belonging to the class of direct-acting oral anticoagulants (DOAC) along with rivaroxoban and edoxaban. Factor Xa is an essential mediator of the clotting pathway in humans. Apixaban is currently approved by the FDA for treatment of VTE, prophylaxis of DVT in patients undergoing knee and hip replacement surgeries and for reducing the risk of embolic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. This study aims to compare the pharmacokinetics and absorption of oral apixaban in patients who have undergone pancreaticoduodenectomy to that of apixaban in historical controls.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreas Cancer, DVT, Pulmonary Embolism
Keywords
apixaban, pancreaticoduodenectomy, whipple, pharmacokinetic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single-dose pharmacokinetic study
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Apixaban dosing
Arm Type
Experimental
Arm Description
Subjects to receive single dose of apixaban
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
Eliquis
Intervention Description
Apixaban is an orally administered highly selective factor Xa inhibitor, belonging to the class of direct-acting oral anticoagulants (DOAC) along with rivaroxoban and edoxaban. Factor Xa is an essential mediator of the clotting pathway in humans. Apixaban is currently approved by the FDA for treatment of VTE, prophylaxis of DVT in patients undergoing knee and hip replacement surgeries and for reducing the risk of embolic stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
Primary Outcome Measure Information:
Title
Serum Apixaban Level
Description
Serum apixaban PK level
Time Frame
0-24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be a male or female between ages 18-65 (inclusive) at the screening visit May have a history of pharmacologically well-controlled hypertension or non-insulin dependent diabetes Have a body mass index (BMI) ≥ 19 and ≤ 33 (inclusive) BMI = (weight (kg))/(height (m2)) Have a history of pancreaticoduodenectomy If female, subject can be of childbearing potential and must demonstrate a urine β-hCG level consistent with the non-gravid state at the screening visit and agree to use (and/or have their partner use) an acceptable method of birth control beginning at the screening visit throughout the trial (including washout intervals between treatment periods) and until 2 weeks after the last dose of trial drug in the last treatment period. Acceptable methods of birth control: intrauterine device ("IUD" with or without local hormone release, oral contraceptive pills, diaphragm, cervical cap, spermicides, contraceptive sponge, and /or condoms). Abstinence is an alternative life style and subjects practicing abstinence may be included in the trial. Can be of non-childbearing potential which is defined as: a female who is postmenopausal without menses for at least 1 year and an FSH value in the postmenopausal range upon screening evaluation and/or a female who is status post hysterectomy, oophorectomy or tubal ligation. Have serum creatinine level < 1.5 mg/dL Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal Have platelet count within normal limits Be willing to refrain from the use of anticoagulants and antiplatelet medications including aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) during the entire period of study participation Be willing to comply with trial restrictions Exclusion Criteria: The subject will be excluded from participating in the trial if the subject: Has a history of clinically significant medical condition that based upon the judgment of the investigator makes participation inappropriate Has a history of a major bleeding event (defined as: (i) symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or (ii) a fall in hemoglobin level of 2 g/dL or more, or leading to transfusion of two or more units of whole blood or red cells) within 6 months prior to screening visit Has had major surgery within 6 months prior to screening visit Is actively taking any the following list of medications/supplements and cannot hold these medications for <5 half-lives prior to the study: CYP3A4 Moderate/Strong Inhibitors: Selective Serotonin Reuptake Inhibitors (SSRI) Amiodarone, Dronedarone Diltiazem Cimetidine Aprepitant Protease Inhibitors CYP3A4 Inducers Rifampin Phenytoin Carbemazepine Ritonavir St. John's Wort Enzalutamide Efavirenz Teriflunomide Bosentan Modafinil Mitotane Other Pancreatic Enzyme Replacement (Creon, Pancrelipase, Viokase) Has a history of illicit drug abuse within six months prior to screening visit Is an active smoker (last exposure <2 weeks prior to study screening) Pregnant or lactating Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day and cannot refrain from alcohol for the duration of the trial Has a history of significant multiple and/or severe allergies (e.g. food, drug), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food Has known anaphylactic or severe systemic reactions to any components of apixaban or contraindication to the administration of apixaban Has moderate or severe hepatic disease or other clinically relevant bleeding risk Use of any drugs or products which at the discretion of the investigator would increase bleeding risk Is considered inappropriate for participation by the investigator for any reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter K Kraft, MD
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thomas Jefferson University Clinical Research Unit
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pharmacokinetics of Apixaban in Patients Undergoing Pancreaticoduodenectomy

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