Phase Ⅰ Clinical Trial of NE-58095 DR, a Risedronate Delayed-Release Tablet: Dose Escalation and Food Effect

抄録

Background: Risedronate is a potent inhibitor of osteoclast-mediated bone resorption. Absorption of risedronate is known to decrease remarkably after meals. Therefore, the conventional immediate-release (IR) tablet must be taken at least 30 min before the first meal of the day, and the patient should refrain from lying down for at least 30 min after taking the IR tablet. NE-58095 DR is a novel risedronate delayed-release (DR) tablet under development to improve absorption and patient adherence. The objective of this study was to perform an exploratory assessment of safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the DR tablet by dose or food effect.

Methods: In the ascending dose stage, the NE-58095 DR dose was sequentially escalated from 25 mg to 75 mg in order to compare it with the conventional 75-mg IR tablet. In the subsequent food effect stage, the effect of food intake on the PK, PD, and safety profiles was investigated at the DR dose that is comparable to the conventional 75-mg IR tablet. The DR tablets were administered immediately after a meal, 30 min before a meal, 30 min after a meal, or under fasting conditions. All subjects were healthy postmenopausal Japanese women.

Results: PK analysis showed that 25- and 37.5-mg DR doses were comparable to the conventional 75-mg IR tablet. Although administration of the 37.5-mg DR tablet under fasting conditions demonstrated the highest exposure and administration immediately after a meal resulted in the lowest exposure, food had no major impact on the PD parameters investigated.

Conclusions: The 25- and 37.5-mg DR tablets exhibited PK profiles comparable to those of the 75-mg IR tablet. There was no influence of meals on the PD parameters of 37.5-mg DR tablet in this clinical trial.