111: Effect of Food on the Pharmacokinetics, Safety & Tolerability of Budesonide Oral Suspension in Healthy Adults: A Randomized Phase 1 Study

Statement of Purpose, Innovation or Hypothesis: Budesonide oral suspension (BOS) 2.0 mg twice daily is a swallowed topical corticosteroid recently approved by the US Food and Drug Administration for 12-week use in patients (≥ 11 years old) with eosinophilic esophagitis. This study aimed to assess the relative bioavailability of budesonide following a single dose of BOS 2.0 mg administered under fasting and fed conditions, as well as the safety and tolerability of BOS, in healthy adults.

Description of Methods & Materials: This was an open-label, randomized, two-period, two-sequence, two-way crossover, phase 1 study in healthy adults (19–55 years old) with a body mass index of 18–32 kg/m². In period 1, participants were randomly assigned to receive a single dose of BOS 2.0 mg under fasting or fed (high-fat/high-calorie meal) conditions. After a washout period of at least 2 days, participants were crossed over to receive a single dose of BOS 2.0 mg under the alternative condition in period 2. Plasma samples for pharmacokinetic (PK) analysis were collected before dosing and up to 24 hours after dosing in each period. For the primary endpoint, the following PK parameters were analyzed for plasma budesonide: maximum observed concentration (C_max), area under the concentration–time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC_last) and AUC from time 0 to infinity, calculated using the observed value of the last quantifiable concentration (AUC_∞). Time to C_max (t_max) was also analyzed as a secondary endpoint. Safety endpoints included the incidence, severity and causality of treatment-emergent adverse events (TEAEs).

Data & Results: A total of 20 participants entered and completed the study, the majority of whom were female (60%), White (55%) and not Hispanic or Latino (85%). Participants had a mean (standard deviation) age of 35.7 (10.0) years and a mean (standard deviation) body mass index of 27.6 (2.7) kg/m². Key plasma budesonide PK parameters are shown in Table 1. After a single dose of BOS 2.0 mg under fed conditions, the geometric mean C_max was ~13% lower and the median t_max was ~1 hour longer (p < 0.001) than under fasting conditions. The geometric mean AUC_last and AUC_∞ were ~26% and ~27% higher, respectively, under fed conditions than under fasting conditions. In total, 10 TEAEs were reported in seven participants (35%; fasting: n = 2; fed: n = 5). All TEAEs were mild in severity, except for one event of headache of moderate severity after BOS administration under fasting conditions. Three participants (15%) had TEAEs considered by the investigator to be related to the study drug. There were no deaths, serious TEAEs or TEAEs leading to study drug discontinuation or study withdrawal.

Interpretation, Conclusion or Significance: Despite slight differences in budesonide PK parameters between fasting and fed conditions, the effect of food on systemic exposure to budesonide (BOS formulation) is not expected to be clinically meaningful. A single dose of BOS 2.0 mg was well tolerated under fasting and fed conditions in healthy adults, with only mild or moderate TEAEs reported and no TEAEs leading to study drug discontinuation or study withdrawal.

Disclosures: This study was funded by Takeda Pharmaceuticals USA, Inc. AJP, JW, NKD, CAR and AS are employees of Takeda Development Center Americas, Inc. VY is an employee of Takeda Pharmaceuticals USA, Inc. All authors are stockholders of Takeda Pharmaceutical Company Limited. Medical writing support was provided by Sarah Graham of PharmaGenesis London, London, UK, and was funded by Takeda Pharmaceuticals USA, Inc.

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