Safety, pharmacokinetics and pharmacodynamics of a novel anti-asthmatic drug, XC8, in healthy probands

Abstract

Introduction: XC8 (histamine glutarimide) is a novel agent which targets eosinophilic migration and mast cell degranulation and has shown anti-asthmatic effects in animal studies. Objective: The objective of this placebo-controlled phase 1 study was to assess the safety of oral XC8 and to evaluate its pharmacokinetic and pharmacodynamic properties. Methods: 32 healthy volunteers in three dose-escalation treatment groups (10 mg [n = 8], 50 mg [n = 8] and 200 mg [n = 16]) were randomized in a 3:1 ratio to XC8 or placebo respectively. The subjects received a single dose of the drug at Day 1 and then once-daily for 14 days (Days 8-21). Results: No severe adverse events occurred. The number of adverse events was similar in the treatment arms compared to placebo and all subjects completed the study as planned. No clinically significant changes occurred in hematologic and biochemical blood tests in subjects receiving XC8. The pharmacokinetic data showed similar dose and time dependent mean plasma XC8 concentrations after single (Day 1) and multiple (Day 21) dosing. The mean maximum concentrations were 114-1993 ng/mL after single and 115-2089 ng/mL after multiple dosing. The mean times to maximum concentration were 0.68-1.01 and 0.67-0.98 h, respectively. There was no evidence for accumulation of XC8 after multiple dosing. Conclusion: XC8 was safe and well tolerated. A phase 2 study is being performed to further evaluate the potential role of XC8 in asthma treatment.

The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs

“…The small molecule drug XC8 (glutarimide derivative) developed by Pharmenterprises LLC was shown to affect the influx of eosinophils into bronchoalveolar lavage (BAL) in a model of lung inflammation or asthma in rats and guinea pigs [ 33 ]. We demonstrated the complete safety of XC8 in healthy probands in phase 1 clinical trial [ 34 ]. In phase 2a trial, we have shown that the treatment of asthma patients with a high levels of blood eosinophils and serum IFN-γ with XC8 led to an improvement in force expiratory volume in 1 s (FEV 1 ) [ 35 ].…”

New Anti-Chemokine Oral Drug XC8 in the Treatment of Asthma Patients with Poor Response to Corticosteroids: Results of a Phase 2A Randomized Controlled Clinical Trial

“…Moreover, we showed that the treatment of mice stimulated with interferon-c (IFNc) with XC8 led to a decrease of neutrophils in the BAL, which correlated with the decrease of C-X-C motif chemokine 10 (CXCL10), known as IFN-c inducible protein (unpublished data). The phase 1 clinical trial of XC8 conducted in Europe in healthy volunteers in three dose-groups (10, 50, and 200 mg) demonstrated its safety [27]. The single and multiple administration of XC8 for up to 14 days demonstrated good tolerability and a favorable safety profile for the dose range 10-200 mg without accumulation.…”