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Venous ThromboembolismPhase 1ACTNCT03083782

Drug Interaction Study of Apixaban With Cyclosporine and Tacrolimus

A Phase 1 study testing Apixaban alone, Cyclosporine and Tacrolimus in people with Venous Thromboembolism and Pharmacokinetics, run by Thomas Jefferson University at 1 site in United States.

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 when co-administered with cyclosporine and tacrolimus in healthy volunteers. The study participants will receive apixaban alone, cyclosporine followed by apixaban and tacrolimus followed by apixaban. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Venous Thromboembolism, Pharmacokinetics, Healthy
What is being tested?
Apixaban alone, Cyclosporine and Tacrolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
18 Apr 2017to 30 Jun 2017
Phase
Phase 1
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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Be a healthy male or female between ages 18-55 (inclusive) at the screening visit
  • Have a body mass index (BMI) ≥ 19 and ≤ 33 (inclusive)
  • Be a female subject, subject
  • Can be of childbearing potential and must demonstrate a urine β-hCG level consistent with the non-pregnancy state and agree to use an acceptable method of birth control throughout the study.
  • Can be of non-childbearing potential.
  • Be a nonsmoker for at least approximately 6 months
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  • 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

Who cannot join

  • Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures), dermatologic or psychiatric abnormalities or diseases
  • Has history of cancer (excluding treated cutaneous squamous or basal cell carcinoma of >3 years previous)
  • Has history of venous or arterial thromboembolic disease
  • 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 unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies for 2 weeks prior to trial start date until the post-trial visit
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  • Is unable to refrain from using any drugs or substance known to be inhibitors or inducers of cytochrome P450 (CYP) enzymes including grapefruit products for 2 weeks prior to dosing and throughout the study, until the post-trial visit
  • Has a history of illicit drug abuse within six months prior to screening visit
  • Pregnant or lactating
  • Consumes greater than 3 glasses of alcoholic beverages 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 study drugs (including apixaban, cyclosporine or tacrolimus) or contraindication to the administration of study drugs
  • Has moderate or severe hepatic disease or other clinically relevant bleeding risk
  • Has positive history for hepatitis B surface antigen, hepatitis C or HIV
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase I, Open-Label, Crossover, Drug Interaction Study of Apixaban With Cyclosporine and Tacrolimus in Healthy Volunteers

This study aims to evaluate the pharmacokinetics (PK) of apixaban when co-administered with cyclosporine and tacrolimus in healthy volunteers. The study participants will receive apixaban alone, cyclosporine followed by apixaban and tacrolimus followed by apixaban.

Read the detailed description

Life- and graft-threatening complications in solid organ transplant patients have been greatly reduced due to the potent immunosuppressive agents like calcineurin inhibitors (CNI) that include cyclosporine and tacrolimus. Venous thromboembolism (clots in legs or lungs) in transplant recipients is often difficult to manage due to polypharmacy and potential for drug interactions. More than 90% of renal transplant (RT) recipients are maintained on a CNI-based immunosuppressive regimen. Cyclosporine is an inhibitor of many metabolic pathways including cytochrome P450 (CYP) 3A4, permeability glycoprotein (P-gp) and, breast cancer resistance protein (BCRP). Tacrolimus shares some of the distributive and metabolic pathways of cyclosporine. Apixaban is a combined substrate of CYP3A4, P-gp and, BCRP and thus has the potential for drug interactions with cyclosporine and tacrolimus. Apixaban levels that are too high or too low could be a problem for transplant patients. The purpose of this study is to determine what happens to apixaban blood levels when given in combination with cyclosporine or tacrolimus.

Being tested
Apixaban alone, Cyclosporine, Tacrolimus, Apixaban
Keywords
Apixaban, Cyclosporine, Tacrolimus, Cytochrome P450 CYP3A4, Permeability Glycoprotein P-gp, Breast cancer resistance protein BCRP, Factor Xa Inhibitors, Anticoagulants, Enzyme Inhibitors
Medical subject headings
Venous Thromboembolism

What participants receive

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

  • Apixaban aloneDrug

    Also called ELIQUIS

    A single dose of 10 mg apixaban administered orally at 0H on Day 1.

  • CyclosporineDrug

    Also called NEORAL

    Once daily dose of 100 mg cyclosporine administered orally on Days 1 to 3.

  • TacrolimusDrug

    Also called PROGRAF

    Once daily dose of 5 mg tacrolimus administered orally on Days 1 to 3.

  • ApixabanDrug

    Also called ELIQUIS

    A single dose of 10 mg apixaban administered orally on Day 3 immediately following cyclosporine

  • ApixabanDrug

    Also called ELIQUIS

    A single dose of 10 mg apixaban administered orally on Day 3 immediately following tacrolimus

Study groups in NCT03083782
Study groupRoleWhat they receive
Treatment A: Apixaban aloneActive comparatorOral apixaban will be administered in healthy volunteers to define baseline apixaban pharmacokinetics
Receives: Drug: Apixaban alone
Treatment B: Cyclosporine with apixabanExperimentalOral cyclosporine will be administered to steady state in healthy volunteers followed by a single oral dose of apixaban to define apixaban pharmacokinetics in the presence of cyclosporine
Receives: Drug: Cyclosporine; Drug: Apixaban
Treatment C: Tacrolimus with apixabanExperimentalOral tacrolimus will be administered to steady state in healthy volunteers followed by a single oral dose of apixaban to define apixaban pharmacokinetics in the presence of tacrolimus
Receives: Drug: Tacrolimus; 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 1-4 (Treatment A), Days 3-6 (Treatment B & C)

  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 1-4 (Treatment A), Days 3-6 (Treatment B & C)

Secondary outcomes (2)

  1. Safety and tolerability of apixaban when co-administered with cyclosporine assessed by capturing adverse events and laboratory safety tests

    Safety and tolerability of apixaban when co-administered with cyclosporine based on adverse events reports and the results of vital sign measurements, electrocardiogram, physical examinations, and clinical laboratory tests

    Measured: Day 1-4 (Treatment A), Day 1-6 (Treatment B & C)

  2. Safety and tolerability of apixaban when co-administered with tacrolimus assessed by capturing adverse events and laboratory safety tests

    Safety and tolerability of apixaban when co-administered with tacrolimus based on adverse events reports and the results of vital sign measurements, electrocardiogram, physical examinations, and clinical laboratory tests

    Measured: Day 1-4 (Treatment A), Day 1-6 (Treatment B & C)

Timeline

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

  1. First posted20 Mar 2017
  2. Study start18 Apr 2017
  3. Primary completion5 Jun 2017
  4. Study completion30 Jun 2017

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 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
Intervention Model: Crossover Assignment
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03083782
Sponsor's protocol ID
10570
Other IDs
BMS-CV185-567
Acronym
ACT
Status last verified
Oct 2017
First submitted
6 Mar 2017
Last updated
11 Oct 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Apixaban alone, Cyclosporine and Tacrolimus in people with Venous Thromboembolism and Pharmacokinetics, run by Thomas Jefferson University at 1 site in United States.

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 11 inclusion and 16 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 11 Oct 2017. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 1-4 (Treatment A), Days 3-6 (Treatment B & C)). 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 NCT03083782.

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 11 Oct 2017.

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