ABSTRACT
Rivaroxaban is an oral anticoagulant that requires food intake at high doses (15 and 20 mg) due to a pronounced food effect. AD‐109 is a novel formulation of rivaroxaban 18 mg, designed to enhance oral bioavailability and mitigate the food effect. This study aimed to evaluate the pharmacokinetics (PKs) of AD‐109 compared to the conventional formulation, Xarelto (Xarelto, rivaroxaban 20 mg) and the effect of food on the PK of AD‐109. Two open‐label, single‐dose, two‐period, two‐sequence crossover studies were conducted. In Study 1, participants received a single dose of AD‐109 and Xarelto under fed state, while in Study 2, participants received a single dose of AD‐109 under fed and fasted state. Serial blood samples were collected up to 34 h post‐dose and PK parameters were calculated by non‐compartmental method. In both studies, 33 out of 36 volunteers completed the study. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for the maximum plasma concentration (C max) and area under the curve until the last measurable concentration (AUC0‐last) of rivaroxaban for AD‐109 to Xarelto were 1.0466 (0.9961–1.0996) and 0.9450 (0.9094–0.9819), falling within the bioequivalence range of 0.8–1.25. The corresponding values of AD‐109 in the fed to fasted state were 1.0475 (0.9789–1.1209) and 0.9795 (0.9371–1.0238), suggesting the systemic exposure was not substantially influenced by food intake. AD‐109 (rivaroxaban 18 mg) demonstrated a PK profile comparable to that of Xarelto (rivaroxaban 20 mg) and effectively minimized the food effect on drug exposure.
Keywords: cardiovascular disease, clinical trials, formulation, pharmacokinetics, phase I
Study Highlights
What is the current knowledge on the topic?
Rivaroxaban is an oral anticoagulant used for the prevention and treatment of thromboembolic disorders. At higher doses like 20 mg, its oral bioavailability is significantly influenced by food intake, requiring administration with meals to ensure consistent systemic exposure.
What question did this study address?
This study evaluated the pharmacokinetics and food effect of AD‐109, a novel formulation of rivaroxaban developed to mitigate the food‐dependent variability of the original 20 mg formulation. Specifically, it assessed whether AD‐109 could (1) demonstrate comparable systemic exposure to Xarelto under fed conditions and (2) maintain consistent pharmacokinetic exposure regardless of food intake.
What does this study add to our knowledge?
AD‐109 showed pharmacokinetic equivalence to Xarelto under fed conditions, despite its lower rivaroxaban content. Moreover, AD‐109 exhibited minimal differences in systemic exposure between fed and fasted states, effectively eliminating the food effect observed with the conventional formulation.
How might this change clinical pharmacology or translational science?
AD‐109 may improve treatment adherence and convenience by allowing flexible dosing without food restrictions. This novel formulation represents a meaningful advancement in oral anticoagulant therapy, offering a patient‐friendly alternative that reduces food‐related variability, potentially enhancing therapeutic outcomes and real‐world effectiveness.
1. Introduction
Thrombosis is a key phenomenon occurring during the hemostasis process. Pathological thrombosis within blood vessels can result in life‐threatening conditions, including venous thrombosis, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thrombosis, such as ischemic stroke and myocardial infarction [1]. The treatment of thrombosis involves the use of a variety of anti‐thrombotic agents, which are categorized into anticoagulants and anti‐platelet agents based on their mechanisms of action [1].
Rivaroxaban, a factor Xa inhibitor, has been approved for its superior effectiveness in managing strokes and embolisms compared to conventional vitamin K antagonists [2, 3, 4, 5]. Four different oral dosage levels of rivaroxaban (2.5, 10, 15, 20 mg) have been approved for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, treating DVT and PE, preventing the recurrence of DVT and PE, and for the prophylaxis of DVT that may lead to PE in patients undergoing knee or hip replacement surgery [6]. Compared to conventional vitamin K antagonists, rivaroxaban carries a lower risk of bleeding‐related adverse effects and potential drug interactions [2, 4]. Additionally, it does not require separate blood sampling for INR monitoring. Furthermore, its shorter half‐life and rapid onset of action offer additional advantages [7, 8].
Rivaroxaban is classified as a Biopharmaceutics Classification System (BCS) Class II drug, characterized by low solubility and high permeability. Clinical studies have demonstrated that exposure to rivaroxaban at lower doses is not substantially affected by food intake, whereas the 15 and 20 mg doses show a pronounced food effect. Consequently, the product label specifies that these higher doses must be administered with food to ensure adequate absorption in clinical practice [6, 7, 9]. While the 10‐mg tablet is almost completely absorbed regardless of food, the 20‐mg tablet exhibits approximately 66% absorption under fasted conditions [6, 7]. Administration with food significantly increases the bioavailability of the 20‐mg dose, with mean AUC and C max increasing by about 39% and 76%, respectively [6]. These findings highlight the limitations associated with the timing of medication intake due to dietary restrictions and the potential variability in absorption caused by food.
To ameliorate the food‐related impacts on the PK and efficacy of the conventional formulation of rivaroxaban 20 mg, a novel formulation of rivaroxaban 18 mg (AD‐109) was developed. This formulation utilizes fluid milling technology to reduce particle size, thereby enhancing dissolution and potentially allowing it to be taken without dietary restrictions.
Two clinical trials were conducted to evaluate the PK and food effect of AD‐109. Study 1 aimed to evaluate the pharmacokinetics and safety of AD‐109 (rivaroxaban 18 mg) compared with Xarelto (Xarelto, rivaroxaban 20 mg) under a fed state. Study 2 focused on assessing the effect of food on the PK profile and safety of AD‐109.
2. Participants and Methods
2.1. Ethics Statement
Study 1, a comparative pharmacokinetics study (NCT05128591) and Study 2, a food effect study (KCT0009335), were both conducted at the H‐plus Yangji Hospital, Seoul, Republic of Korea. Both studies were performed in accordance with the ethical principles outlined in the Declaration of Helsinki and its amendments, the International Conference on Harmonization (ICH) Guidelines, and Korean Good Clinical (KGCP) guidelines. The study protocols were reviewed and approved by the Institutional Review Board (IRB) of H‐plus Yangji Hospital and the Ministry of Food and Drug Safety (MFDS). Written informed consent was obtained from all participants prior to any study‐related procedures.
2.2. Study Population
In both Study 1 and Study 2, healthy volunteers aged 19 years or older, with a body mass index (BMI) between 18 and 30 kg/m2, and in good health based on medical history, physical examination, and laboratory screening, were eligible to participate.
Main exclusion criteria for both studies included the presence of clinically significant diseases, such as cardiovascular, gastrointestinal, hepatic, renal, or hematologic disorders, as well as any history of clinically significant bleeding, including intracranial or gastrointestinal hemorrhage. Participants with a history of gastrointestinal surgery that could affect drug absorption, or those who had taken enzyme‐inducing or enzyme‐inhibiting drugs within 1 month of the first dosing, were excluded. Additional criteria included participation in another clinical trial within 6 months, or a history of hypersensitivity to the study drug or its components. Participants with conditions increasing the risk of bleeding, such as recent gastrointestinal ulcers, intracranial hemorrhage, or significant hepatic impairment (Child‐Pugh B or C), were also excluded.
2.3. Study Design
Two separate clinical studies were conducted, both utilizing an open‐label, randomized, 2‐sequence, 2‐period, crossover design (Figure 1). In Study 1, a single dose of AD‐109 or Xarelto was administered to evaluate the PK and safety of AD‐109 under the fed state compared to Xarelto in healthy male participants. Participants were randomly assigned to one of two sequences: AD‐109 followed by Xarelto or Xarelto followed by AD‐109, with a 7‐day washout between treatments. Study 2 aimed to assess the food effect on the PK and safety of AD‐109, where participants received a single dose of AD‐109 under fed and fasted conditions in a crossover manner. Participants in this study were also randomly assigned to one of two treatment sequences: fed followed by fasted or fasted followed by fed, with a 7‐day washout period between treatments. The washout period was set as 7 days in both studies, considering the reported terminal half‐life of 5–9 h [7].
FIGURE 1.
Study overview of (A) Study 1 (comparative pharmacokinetics study; NCT05128591) and (B) Study 2 (food effect study; KCT0009335). AD‐109, rivaroxaban 18 mg tablet; Xarelto, xarelto rivaroxaban 20 mg. *The washout period was set to 7 days between each dosing.
Under fasted states, participants were required to abstain from food for at least 10 h overnight before dosing, and the study drug was administered with 150 mL of water. Participants were restricted from food and drink for at least 4 h post‐dose. Under fed states, participants also fasted for at least 10 h overnight, followed by the administration of the study drug with 150 mL of water after consuming a high‐fat breakfast containing ≥ 900 kcal and ≥ 35% lipid content. Participants were instructed to finish breakfast within 20 min, starting 30 min prior to dosing.
2.4. Study Drugs
AD‐109 (rivaroxaban 18 mg per tablet) was manufactured by Yuhan Co. Ltd., with a batch number of 21001. Xarelto (rivaroxaban 20 mg per tablet) was manufactured by Bayer with a batch number of BXJJPC1.
2.5. PK Sample Preparation
Approximately 7 mL of blood samples were collected serially at each timepoint to analyze the plasma concentration of rivaroxaban. In Study 1, blood samples were collected prior to dosing (0 h) and at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, and 34 h post‐dose. In Study 2, the PK sampling schedule was identical to that of Study 1, with additional samples collected at 0.5 and 0.75 h post‐dose. All blood samples were centrifuged at 3000 rpm for 10 min at 4°C. The supernatant plasma was separated and stored at temperatures below −70°C until analysis.
2.6. Bioanalytical Methods
The bioanalysis of rivaroxaban was conducted at the Clinical Trials Center of Kyungpook National University using a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Sample preparation involved protein precipitation for rivaroxaban with 800 μL of formic acid/acetonitrile (1:100, v/v). The ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) system was equipped with an ACQUITY UPLC BEH C18 column (2.10 × 50 mm). Gradient elution was performed using two mobile phases: formic acid/water (1:1000) and formic acid/acetonitrile (1:1000), with a flow rate of 0.25 mL/min. The internal standard (IS) was a deuterated isotope of rivaroxaban (rivaroxaban‐d4). Detection was carried out using positive electrospray ionization in multiple reaction monitor (MRM) mode. The MRM transitions were m/z 436.0 to 145.0 for rivaroxaban and m/z 440.0 to 145.0 for the IS. Calibration standards were validated over a concentration range of 2.0–800 ng/mL. The lower limit of quantification was 2.0 ng/mL.
2.7. Pharmacokinetic Evaluation
PK parameters were calculated using a noncompartmental analysis (NCA) model in WinNonlin Version 8.0 or 8.3 (Certara USA, Princeton, New Jersey), under the assumption of a log‐linear terminal phase, and were summarized using descriptive statistics. The primary PK parameters included the maximum plasma concentration (C max) and the area under the plasma concentration‐time curve (AUC) from time 0 to the last measurable concentration (AUC0‐last). The AUC0‐last was determined using the linear trapezoidal method for the ascending concentrations and the log trapezoidal method for descending concentrations. Additionally, the AUC from time zero to infinity (AUCinf), time to achieve C max (T max), terminal half‐life (t 1/2) were also evaluated.
2.8. Safety Evaluation
Safety evaluation encompassed various criteria, including treatment‐emergent adverse events (TEAEs), vital signs, physical examinations, and clinical laboratory tests. The severity of TEAEs was categorized as mild, moderate, or severe. The causal relationship with the investigational products was assessed as “Certain,” “Probable,” “Possible,” “Unlikely,” “Definitely Not,” and “Unassessable,” considering factors such as the temporal relationship between drug administration and the event, as well as the mechanism of action of the investigational products.
2.9. Statistical Analysis
Statistical analyses were conducted using SAS 9.4 (SAS Institute Inc., Cary, North Carolina). In Study 1, the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the C max, AUC0‐last, and AUCinf of rivaroxaban were calculated using a linear mixed‐effects model. The fixed effects included sequence, period, and treatment, while the random effect was set as subject nested within sequence. In Study 2, the GMR and 90% CIs for the C max, AUC0‐last, and AUCinf of rivaroxaban were calculated with a generalized linear model. The model included treatment, period, sequence, sequence nested subject random effect.
Study 1 compared the PK of rivaroxaban following administration of AD‐109 to that of Xarelto. Study 2 evaluated the effect of food on the PK parameters of rivaroxaban after administration of AD‐109 by comparing the fed state to the fasted state.
3. Results
3.1. Subject Disposition and Demographics
In Study 1, a total of 38 participants were randomized, of whom 33 completed the study as planned (Figure 2). All 33 participants who completed the study were included in the PK analysis set, while the safety analysis set comprised all 36 participants who received at least one dose of the investigational products. The mean age and the BMI were 28.67 years and 23.95 kg/m2, respectively (Table 1).
FIGURE 2.
Subject disposition of (A) Study 1 and (B) Study 2. *Dropout due to treatment‐emergent adverse events. Xarelto, xarelto rivaroxaban 20 mg.
TABLE 1.
Baseline demographic characteristics.
| Characteristics | Study 1 (N = 36) | Study 2 (N = 36) |
|---|---|---|
| Age (year) | 28.67 ± 9.51 | 25.75 ± 7.55 |
| Height (cm) | 175.71 ± 5.77 | 167.41 ± 9.28 |
| Body weight (kg) | 74.11 ± 9.79 | 64.72 ± 13.11 |
| BMI (kg/m2) | 23.95 ± 2.47 | 22.89 ± 2.93 |
| Sex | ||
| Male, n (%) | 36 (100.0) | 20 (55.6) |
| Female, n (%) | — | 16 (44.4) |
| Ethnicity | ||
| Asian, n (%) | 36 (100.0) | 36 (100.0) |
Note: Values are presented as arithmetic mean ± standard deviation.
Abbreviation: BMI, body mass index.
In Study 2, a total of 38 participants were randomized, and 33 completed the study as planned (Figure 2). Similarly, all 33 subjects who completed the study were included in the PK analysis set, while the safety analysis set consisted of all 36 who received at least one dose of the investigational product. The mean age and the BMI were 25.75 years and 22.89 kg/m2, respectively (Table 1).
3.2. Pharmacokinetics
In Study 1, the PK profiles of rivaroxaban were similar between AD‐109 and Xarelto (Figure 3). The median T max was 2.00 for AD‐109 and 2.50 h for Xarelto, while the mean t 1/2 was 6.58 and 7.51 h, respectively (Table 2). The GMRs (90% CIs) for C max and AUC0‐last were 1.0466 (0.9961–1.0996) and 0.9450 (0.9094–0.9819), respectively (Table 2). These values fell within the bioequivalence range of 0.80 to 1.25.
FIGURE 3.
Mean plasma concentration‐time profiles of rivaroxaban after a single oral administration of AD‐109 or Xarelto under “fed” state. Plasma concentration‐time profile until 12 h is inserted as inset figures. Error bars present standard deviation; AD‐109, rivaroxaban 18 mg tablet; Xarelto, xarelto rivaroxaban 20 mg.
TABLE 2.
Pharmacokinetic parameters of rivaroxaban in Study 1, after a single administration of AD‐109 or Xarelto under fed state.
| PK parameters | Xarelto (N = 33) | AD‐109 (N = 33) | GMR a (90% CIs) |
|---|---|---|---|
| T max (h) | 2.50 [1.00–5.00] | 2.00 [1.00–6.00] | |
| C max (μg/L) | 309.70 ± 76.26 | 320.43 ± 59.83 | 1.0466 (0.9961–1.0996) |
| AUC0‐last (h·μg/L) | 2360.95 ± 600.11 | 2208.58 ± 434.04 | 0.9450 (0.9094–0.9819) |
| AUCinf (h·μg/L) | 2457.23 ± 617.15 | 2272.58 ± 451.75 | 0.9333 (0.9010–0.9668) |
| CL/F (L/h) | 8.26 ± 1.86 | 8.60 ± 2.02 | |
| V d/F (L) | 77.74 ± 30.25 | 94.26 ± 41.41 | |
| t 1/2 (h) | 7.51 ± 2.44 | 6.58 ± 2.02 |
Note: Values are presented as arithmetic mean ± standard deviation.
Abbreviations: AD‐109, rivaroxaban 18 mg tablet; AUC0‐last, area under the plasma concentration‐time curve from time zero to the last quantifiable concentration time; AUCinf, area under the plasma concentration‐time curve from time to infinity; CIs, confidence intervals; CL/F, apparent clearance; C max, maximum plasma concentration; GMR, geometric mean ratio; t 1/2, terminal elimination half‐life; V d/F, apparent volume of distribution; Xarelto, xarelto rivaroxaban 20 mg.
Geometric mean ratio of AD‐109 to Xarelto.
In Study 2, the PK profiles of rivaroxaban were comparable between the fasted state and the fed state (Figure 4). The median T max was 2.16 under fasted states and 2.50 h under fed states respectively, while the mean t 1/2 was 8.44 and 5.85 h, respectively (Table 3). The GMRs (90% CIs) of C max and AUC0‐last were 1.0475 (0.9789–1.1209) and 0.9795 (0.9371–1.0238), respectively, suggesting that food did not significantly alter the overall exposure of rivaroxaban (Table 3).
FIGURE 4.
Mean plasma concentration‐time profiles of rivaroxaban after a single oral administration of AD‐109 under fed or fasted state. Plasma concentration‐time profile until 12 h is inserted as inset figures. Error bars present standard deviation; AD‐109, rivaroxaban 18 mg tablet; Xarelto, xarelto rivaroxaban 20 mg.
TABLE 3.
Pharmacokinetic parameters of rivaroxaban in Study 2, after a single administration of AD‐109 under fed or fasted state.
| PK parameters | Fasted (N = 33) | Fed (N = 33) | GMR a (90% CIs) |
|---|---|---|---|
| T max (h) | 2.50 [0.75–4.50] | 2.00 [1.00–4.50] | |
| C max (μg/L) | 356.15 ± 78.40 | 370.35 ± 64.22 | 1.0475 (0.9789–1.1209) |
| AUC0‐last (h·μg/L) | 2463.39 ± 448.27 | 2419.75 ± 479.95 | 0.9795 (0.9371–1.0238) |
| AUCinf (h·μg/L) | 2595.71 ± 524.59 | 2468.27 ± 489.73 | 0.9510 (0.9084–0.9956) |
| CL/F (L/h) | 7.22 ± 1.49 | 7.58 ± 1.54 | |
| V d/F (L) | 84.97 ± 28.66 | 63.32 ± 19.56 | |
| t 1/2 (h) | 8.44 ± 3.44 | 5.85 ± 1.53 |
Note: Values are presented as arithmetic mean ± standard deviation.
Abbreviations: AD‐109, rivaroxaban 18 mg tablet; AUC0‐last, area under the plasma concentration‐time curve from time zero to the last quantifiable concentration time; AUCinf, area under the plasma concentration‐time curve from time to infinite; CIs, confidence intervals; CL/F, apparent clearance; C max, maximum plasma concentration; GMR, geometric mean ratio; t 1/2, terminal elimination half‐life; V d/F, apparent volume of distribution; Xarelto, xarelto rivaroxaban 20 mg; Xarelto, xarelto rivaroxaban 20 mg.
Geometric mean ratio of “Fed” state to “Fasted” state.
3.3. Safety
In Study 1, a total of 2 TEAEs were reported in 2 of 35 participants (5.71%) who received Xarelto, and 1 TEAE was reported in 1 of 34 subjects (2.94%) who received AD‐109 (Table S1). All observed TEAEs, including those leading to the discontinuation of 2 participants, were classified as mild to moderate in severity, and their relationship with the investigational products was deemed “unlikely.” No serious adverse events (SAEs) were reported after the administration of either AD‐109 or Xarelto.
In Study 2, a total of 7 TEAEs were reported in 5 of 34 participants (14.7%) who received AD‐109 under fasted states, and 5 TEAEs were reported in 5 of 35 participants (14.3%) under fed states. Three participants discontinued the study due to TEAEs, but all reported TEAEs, including those leading to discontinuation, were classified as mild to moderate in severity, with their relationship to the investigational product also deemed “unlikely.” No SAEs were observed following the administration of AD‐109 under either fed or fasted states.
4. Discussion
Drugs are categorized by the BCS class based on their solubility and permeability [10]. Rivaroxaban, classified as a BCS class II drug, exhibits low solubility and high permeability. Various strategies have been employed to enhance the absorption of BCS class II drugs by improving solubility [11, 12, 13, 14, 15]. Reducing particle size is one effective approach, as increased surface area per unit volume enhances solubility and subsequently improves absorption [16]. AD‐109, developed using fluid energy mill technology, successfully reduced the particle size, potentially improving solubility. In vitro dissolution tests demonstrated that AD‐109 and Xarelto exhibited comparable dissolution profiles under fasted state simulated intestinal fluid (FaSSIF). However, in the fed state simulated intestinal fluid (FeSSIF), AD‐109 showed a consistently higher dissolution rate than Xarelto across all time points, with a notably smaller difference between fasted and fed conditions (unpublished data). These findings suggest that AD‐109 may offer improved dissolution under fed conditions and reduced sensitivity to food, thereby enhancing systemic absorption consistency.
Although a 3 × 6 crossover design could accommodate both the comparative PK evaluation and the assessment of food effect, given that the AD‐109 fed treatment arm was common to both studies, the trials were conducted separately for methodological and ethical reasons. A 3‐period design would extend the study duration per participant, increase the risk of dropout, and expose participants to repeated drug administration, which may raise ethical and safety concerns. In contrast, the stepwise approach allowed the decision to proceed with the food effect study to be informed by the results of the initial comparative PK analysis. This design minimized unnecessary drug exposure and supported efficient resource utilization while maintaining scientific rigor.
Regulatory guidelines recommend controlling food ingestion during clinical bioequivalence studies to minimize PK variability. Reflecting the clinical application of Xarelto, which is approved for administration under “fed” states to improve bioavailability, Study 1 compared the PK and safety of AD‐109 and Xarelto under “fed” states, specifically following a high‐fat meal.
The results of Study 1 demonstrated the PK similarity between AD‐109 and Xarelto, with GMRs and their 90% CIs of C max and AUC0‐last falling within the bioequivalence range of 0.80–1.25. These findings suggest that AD‐109 achieves systemic exposure levels comparable to Xarelto despite its lower rivaroxaban content.
The reference drug Xarelto exhibits a significant food effect on its PK. The absolute bioavailability of rivaroxaban 20 mg is reported to be < 70% under the fasted state [9]. Administering Xarelto with food significantly increases bioavailability, leading to a 39% and 76% increase in the mean AUC and C max, respectively [9]. In contrast, AD‐109 was designed to mitigate the food effect by improving solubility under the fasted state, thereby enhancing bioavailability under the fasted state. Results from Study 2 demonstrated a significant improvement in the bioavailability of rivaroxaban under fasted states with AD‐109, resulting in negligible differences in overall systemic exposure between fed and fasted states.
In both studies, a statistically significant difference in t 1/2 was observed in Study 1 (p = 0.0200), and Study 2 (p < 0.0001), based on the Wilcoxon signed‐rank test. However, such findings are consistent with previously reported clinical studies of rivaroxaban and are likely attributable to flip‐flop kinetics. Considering the known absorption rate variability of rivaroxaban, the observed statistical differences in t 1/2 are not considered clinically meaningful [7, 9]. Notably, despite the statistical difference in t 1/2, AD‐109 demonstrated comparable systemic exposure to Xarelto under the fed condition in Study 1, and similar exposure between fed and fasted states in Study 2, supporting both its PK equivalence to the reference product and reduced sensitivity to food effects.
AD‐109, a novel formulation of rivaroxaban 18 mg, demonstrated PK equivalence to Xarelto with rivaroxaban 20 mg under fed conditions. Additionally, AD‐109 showed negligible differences in systemic exposure between fed and fasted states, effectively mitigating the food effect observed in the original formulation.
Author Contributions
All authors wrote the manuscript. T.L. and J.K. designed the research. T.L. and J.K. performed the research. H.R. analyzed the data.
Funding
This study was funded by Addpharma Co. Ltd., and Yuhan Corporation. This study was also supported by the Industrial Strategic Technology Development Program (20014907, CIS region and ASEAN market entry‐type medicinal efficacy and bio‐efficiency enhancement Nano‐based improved pharmaceutical product technology development) funded by the Ministry of Trade Industry & Energy (MOTIE, Korea).
Conflicts of Interest
Taewon Lee and Jandee Kim are full‐time employees of Addpharma Co. Ltd. The other authors declare no conflicts of interest.
Supporting information
Table S1: cts70439‐sup‐0001‐TableS1.docx.
Ryu H., Cho J.‐Y., Lee T., Kim J., and Lee S., “Assessment of Pharmacokinetics and Food Effect of AD‐109, a Novel Formulation of Rivaroxaban 18 mg,” Clinical and Translational Science 18, no. 12 (2025): e70439, 10.1111/cts.70439.
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Associated Data
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Supplementary Materials
Table S1: cts70439‐sup‐0001‐TableS1.docx.