What is the clinical evidence from this study?

Study design: RCT. Population: Healthy volunteers (n=32). Intervention: Edoxaban (fed state) vs. Fasted state. Primary outcome: Pharmacokinetics (AUC(0-t), AUC(0-∞), and C(max)) (6% to 22% increase).

June 10, 2010

Effects of Food on the Pharmacokinetics of Edoxaban, an Oral Direct Factor Xa Inhibitor, in Healthy Volunteers

Key Result

Administration of edoxaban 60 mg with a high-fat meal resulted in modest, clinically insignificant increases in pharmacokinetic parameters (6% to 22%) compared to the fasted state.

Study Design

Type

RCT (n=32)

Blinding

Open-label

Randomization

Crossover

Structured PICO

Does a standard high-fat meal affect the pharmacokinetics of a single 60 mg dose of edoxaban in healthy male volunteers?

Population

32 healthy Japanese and Caucasian male volunteers matched by body mass index

Intervention

Single-dose (60 mg) edoxaban administered with a standard high-fat meal (fed state)

Comparator

Single-dose (60 mg) edoxaban administered in a fasted state (2-period crossover)

Outcome

Pharmacokinetics (PK) of edoxaban, specifically geometric mean ratios (fed/fasted) for AUC(0-t), AUC(0-∞), and C(max)surrogate

Edoxaban can be administered without regard to food, as a high-fat meal produces only modest, clinically insignificant increases in its pharmacokinetic parameters.

Main Result

Effect estimate: 6% to 22% increase

Abstract

The primary objective of this study was to assess the effect of a standard high-fat meal on the single-dose (60 mg) pharmacokinetics (PK) of edoxaban in healthy Japanese and Caucasian male volunteers matched by body mass index. This was an open-label, randomized, 2-period crossover study. All 32 enrolled volunteers completed the study per protocol. Both serial blood and urine samples were collected, and edoxaban concentrations were analyzed by a validated liquid chromatography/tandem mass spectrometry method. Activated partial thromboplastin and prothrombin times were obtained as measures of pharmacodynamic effect. The point estimates of the geometric mean ratios (fed/fasted) for AUC(0-t), AUC(0-∞), and C(max) demonstrated modest increases ranging from 6% to 22% across PK parameters for both race cohorts. The disposition was similar in both Japanese and Caucasian matched volunteers with slightly higher AUC values (ranging from 7%-9%) in Caucasians. There were no serious adverse events during the study. All drug-related adverse events were mild and self-limited, and none were bleeding related. Both Japanese and Caucasian volunteers demonstrated a modest but clinically insignificant food effect. It was concluded that edoxaban can be administered without regard to food.

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