Phase 1 trial of a novel chemokine inhibitor

XC8 (histamine glutarimide) is a non-steroidal anti-inflammatory anti-bronchoconstriction agent which targets eosinophilic migration and mast cell degranulation by inhibition of chemokines (CCL2, CCL7, CCL8, CCL13). Previous animal studies have shown beneficial effects of XC8 on airway inflammation. The primary objective of this double-blind placebo-controlled multi-center dose-escalating phase-1 study was to assess the safety of oral XC8. The secondary objective was evaluating the pharmacokinetics (PK). The study population consisted of 32 healthy female (47%) and male adults. Three dose-escalation cohorts (10 mg [n=8], 50 mg [n=8] and 200 mg [n=16]) in two centers were randomized in a 3:1 ratio. The subjects received a single dose at Day 1 and then once-daily for 14 days (Days 8-21). Safety data was collected until Day 36. PK data were collected before (Days 1 and 8-21) and 20 min, 30 min, 1, 2, 4, 8 and 24h after (Days 1 and 21) the administration of the investigational product, respectively. No severe adverse events (AE) occurred. No AEs led to study discontinuation, all subjects completed the study as planned. AEs were not increased in the treatment arms compared to placebo. No clinically significant changes occurred in the safety laboratory in subjects receiving XC8. The PK data showed similar dose and time dependent mean plasma XC8 concentrations both after single (Day 1) and multiple (Day 21) dosing. The median time to maximum plasma concentration was 0.68-1.01 hours after single and 0.67-0.98 hours after multiple dosing. There was no evidence for accumulation of XC8 and it showed linear PK. XC8 was safe and well tolerated. A phase 2 study will be performed to further evaluate the potential role of XC8 in asthma treatment.