R411 is an oral, dual ⍺4/β1 and ⍺4/β7 integrin antagonist being developed as an asthma controller. The objective of this study was to investigate the safety, tolerability, and pharmacokinetics of R411 after oral administration as single ascending doses.

Seven groups of 10 subjects each received single oral doses of R411 in a randomized, double-blind, parallel, placebo-controlled, ascending adaptive dose design. Each group of subjects received 1 of 7 oral doses (10, 50, 150, 300, 600, 900, and 1200 mg) under fasted conditions. Serial blood samples were collected at selected time points. Pharmacokinetic parameters were measured by monitoring RO0270608, the active metabolite of R411, using a noncompartmental approach. Safety and tolerability were assessed by monitoring adverse events, vital signs, ECG, physical examination, and laboratory parameters.

After single ascending oral doses, the C_max of RO0270608 ranged from 35 μg/L for 10mg dose to 2021 μg/L for 1200 mg dose with t_max of 1–2 hr. The exposure (AUC_0-∞) increased proportionally with the dose and was linear in the 150–1200 mg interval (p>0.05). Terminal t_1/2 was about 7–9 hr. No serious adverse events were reported, and overall adverse events were comparable to placebo.

The pharmacokinetics of R411 were linear, dose proportional, and compatible with once-daily dosing. R411 was well tolerated with no safety concerns.