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PharmacokineticsPhase 4ACT-KLRNCT04023760

Drug Interaction Study of Apixaban With Cyclosporine or Tacrolimus in Transplant Recipients

A Phase 4 study testing Apixaban in people with Pharmacokinetics and Kidney Transplant, run by University of Saskatchewan at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study aims to evaluate the pharmacokinetics (PK) of apixaban in kidney and lung transplant recipients stabilized on either cyclosporine or tacrolimus as part of their immunosuppressive therapy. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Apixaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteCanada
Study dates
26 Jun 2019to 30 Mar 2020
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Kidney or lung transplant patients followed as outpatients who are currently stabilized on immunosuppressive therapy with tacrolimus or cyclosporine
  • Age 18 or older
  • At least six months after transplantation
  • Lack of transplant rejection within the last 12 weeks
  • Creatinine clearance at least above 15ml/min as calculated by Cockroft-Gault formula
  • Negative urine pregnancy test for female patients of childbearing potential
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  • Consent to the study
  • Be a nonsmoker for at least approximately 6 months prior to the study
  • Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal
  • Have a hemoglobin level of above at least 80g/L
  • Be willing to refrain from the use of anticoagulants and antiplatelet medications including aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) for two weeks prior and during the entire period of study participation
  • Be willing to avoid drinking grapefruit juice or consuming natural health products for two weeks prior and during the study period
  • Be willing to avoid alcohol and cannabis for 48 hours before the study and for the entire duration of the study
  • Be willing to comply with trial restrictions
  • Be deemed safe to participate by the study physician

Who cannot join

  • Patients on antiplatelet therapy for any cardiovascular treatment (such as clopidogrel, prasugrel, ticagrelor). Patients on prophylactic aspirin will be eligible otherwise.
  • Patients not receiving tacrolimus or cyclosporine
  • A history of an anaphylactic or severe systemic reactions to apixaban
  • Any form of substance abuse or major untreated psychiatric disorder
  • Pregnancy or lactation
  • Tacrolimus or cyclosporine changes within the last two weeks
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  • Receiving concurrent therapy with warfarin, or are taking medications known to be strong inhibitors of both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) such as azole-antimycotics antifungals (e.g., ketoconazole, voriconazole.)
  • Has congenitial or acquired coagulation disorders
  • 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
  • Has any unstable medical condition that could interfere with the study
  • Is considered inappropriate for participation by the investigator for any reason
  • Clinically significant active bleeding, including gastrointestinal bleeding
  • Lesions or conditions at increased risk of clinically significant bleeding, e.g., recent cerebral infarction (ischemic or hemorrhagic), active peptic ulcer disease with recent bleeding, patients with spontaneous or acquired impairment of hemostasis
  • Patients who donate blood within 56 days of participating in the study

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Saskatchewan Health Authority

    Saskatoon, Saskatchewan

Other trials in Canada

About this study

Official title: Pharmacokinetics of Apixaban and Tacrolimus or Cyclosporine in Kidney and Lung Transplant Recipients

This study aims to evaluate the pharmacokinetics (PK) of apixaban in kidney and lung transplant recipients stabilized on either cyclosporine or tacrolimus as part of their immunosuppressive therapy.

Read the detailed description

Solid organ transplantation is a lifesaving option for many patients with end-stage organ disease. After transplant surgery, patients must take immunosuppressive therapy, which carries significant risk for drug-drug interactions and adverse medication-related events.

Transplant recipients are at an increased risk for co-morbidities traditionally managed with warfarin, such as venous thromboembolism and atrial fibrillation. Apixaban has the potential to provide safer and more effective treatment, without additional monitoring of the INR, but it has not been studied in conjunction with anti-rejection agents in this population. Apixaban is metabolized by CYP3A4 and P-gp and BCRP transporters. As part of their immunosuppressive therapy, solid organ transplant recipients are maintained on calcineurin inhibitors, which are weak CYP3A4 as well as potent P-gp and BCRP inhibitors. A study was recently undertaken to evaluate the potential drug-drug interaction between cyclosporine or tacrolimus and apixaban in healthy subjects (ClinicalTrials.gov Identifier: NCT03083782) . The results indicated that the change in apixaban exposure was not clinically relevant.

PK studies in healthy volunteers are a first step for determining the nature and extent of potential drug-drug interactions. However, follow-up studies in the actual patient populations are essential for ensuring safety and tolerability, and providing clinicians the confidence to use these combinations. The purpose of this study is to confirm the pharmacokinetic characteristics and safety of apixaban in combination with tacrolimus and cyclosporine in stable kidney and lung transplant recipients.

Being tested
Apixaban

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApixabanDrug

    Also called Eliquis

    Study subjects given a single-dose of apixaban 10 mg.

Study groups in NCT04023760
Study groupRoleWhat they receive
Treatment group A: Cyclosporine in transplant recipientsExperimentalA single oral dose of 10 mg apixaban will be administered to kidney or lung transplant recipients stabilized on cyclosporine as part of their immunosuppressive regimen
Receives: Drug: Apixaban
Cyclosporine in healthy subjectsActive comparatorResults from Treatment group A will be compared to previously obtained data in healthy participants receiving a single dose of apixaban with a daily dose of 100 mg of cyclosporine at steady state concentration (Bashir et al. Clin Transl Sci. 2018 Jul 3. doi: 10.1111/cts.12580) Transplant recipients require continuous immunosuppression so it will not be possible to stop the cyclosporine or tacrolimus to serve as a control. As such PK plasma time curves will be compared to data in healthy volunteers.
Receives: Drug: Apixaban
Treatment group B: Tacrolimus in transplant recipientsExperimentalA single oral dose of 10 mg apixaban will be administered to kidney or lung transplant recipients stabilized on tacrolimus as part of their immunosuppressive regimen
Receives: Drug: Apixaban
Tacrolimus in healthy subjectsActive comparatorResults from Treatment group B will be compared to previously obtained data in healthy participants receiving a single dose of apixaban with a daily dose of 100 mg of tacrolimus at steady state concentration (Bashir et al. Clin Transl Sci. 2018 Jul 3. doi: 10.1111/cts.12580) Transplant recipients require continuous immunosuppression so it will not be possible to stop the cyclosporine or tacrolimus to serve as a control. As such PK plasma time curves will be compared to data in healthy volunteers.
Receives: Drug: Apixaban

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Apixaban area under the plasma concentration curve between 0 and 72 hours (AUC(0-72)).

    Blood samples for Apixaban pharmacokinetics will be collected prior to apixaban administration at 0H, and then at 1, 2, 3, 4, 6, 12, 24, 48 and, 72 hours in each treatment arm

    Measured: Days 1-3

  2. Apixaban peak plasma concentration (Cmax)

    Blood samples for Apixaban pharmacokinetics will be collected prior to apixaban administration at 0H, and then at 1, 2, 3, 4, 6, 12, 24, 48 and, 72 hours in each treatment arm.

    Measured: Days 1-3

Secondary outcomes (2)

  1. Safety and tolerability of Apixaban when co-administered with cyclosporine assessed by capturing incidence of adverse events

    Number of participants who experience an adverse events based on the results of laboratory safety tests and the results of vital sign measurements, physical examinations, and clinical laboratory tests

    Measured: Days 1-4

  2. Safety and tolerability of Apixaban when co-administered with tacrolimus assessed by capturing incidence of adverse events

    Number of participants who experience an adverse events based on the results of laboratory safety tests and the results of vital sign measurements, physical examinations, and clinical laboratory tests

    Measured: Days 1-4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2019
  2. Study start26 Jun 2019
  3. Primary completion30 Mar 2020
  4. Study completion30 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04023760
Sponsor's protocol ID
99861
Acronym
ACT-KLR
Status last verified
Apr 2021
First submitted
28 Jun 2019
Last updated
3 May 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Bashir B, Stickle DF, Chervoneva I, Kraft WK. Drug-Drug Interaction Study of Apixaban with Cyclosporine and Tacrolimus in Healthy Volunteers. Clin Transl Sci. 2018 Nov;11(6):590-596. doi: 10.1111/cts.12580. Epub 2018 Jul 27.

    PubMed 29972633

  • Mansell H, Shoker A, Alcorn J, Fenton ME, Tam JS, Semchuk W, Bashir B, Kraft WK, Yao S, Douketis JD. Pharmacokinetics of apixaban and tacrolimus or cyclosporine in kidney and lung transplant recipients. Clin Transl Sci. 2022 Jul;15(7):1687-1697. doi: 10.1111/cts.13284. Epub 2022 May 2.

    PubMed 35439353

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Apixaban in people with Pharmacokinetics and Kidney Transplant, run by University of Saskatchewan at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Apixaban area under the plasma concentration curve between 0 and 72 hours (AUC(0-72)). (time frame: Days 1-3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04023760, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021.

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