Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Breast Neoplasms

Thromboembolism

Venous Thromboembolism

Thrombosis

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Embolism and Thrombosis

Vascular Diseases

Anti-Infective Agents

Antirheumatic Agents

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All Drugs and Chemicals

Anticoagulants

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Amino Acids

Cyclosporine

Cyclosporins

Tacrolimus

Apixaban

Factor Xa Inhibitors

Enzyme Inhibitors

polysaccharide-K

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

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Antithrombin III

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Serine Proteinase Inhibitors

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Serine

Oral apixaban will be administered in healthy volunteers to define baseline apixaban pharmacokinetics

Oral 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

Oral 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

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

Apixaban alone

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

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

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

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

Walter K Kraft, M.D.

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.

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.

Drug Interaction Study of Apixaban With Cyclosporine and Tacrolimus

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

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.

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

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

Spots Global Cancer Trial Database for cytochrome p450 cyp3a4