A subgroup of 18 old volunteers (8 male and 10 female subjects; age range, 65-77 years; median age, 69 years) were subjected to VZV antigen skin testing, as described above. Approximately 2 to 3 months later, volunteers received 15 mg of Losmapimod (GW856553) twice daily for 4 days (provided by GlaxoSmithKline under a Medical Research Council Industrial Collaboration Agreement). The dose of 15 mg of Losmapimod twice daily used in this study was chosen on the basis of the pharmacokinetic, pharmacodynamic, and safety profiles of Losmapimod observed in GlaxoSmithKline phase I and II studies.15 (link)
On day 4 of Losmapimod treatment, VZV skin test antigen was injected intradermally, and clinical scores were recorded 48 hours later, as before. A history of liver disease or increased liver transaminase levels (>1.5 times the upper limit of normal) and abnormal electrocardiographic results were additional exclusion criteria for this part of the study. Serum CRP levels were measured by using a high-sensitivity assay.16 (link)
To assess compliance, ex vivo whole-blood LPS stimulation assays were performed before and 4 days after Losmapimod treatment.17 (link) Briefly, peripheral blood was cultured with LPS (0-1 mg/mL) for 24 hours (37°C in a 5% CO2 atmosphere). Levels of TNF-α and IL-6 in plasma were assessed by using the Cytometric Bead Array (CBA; BD, San Jose, Calif).
On day 4 of Losmapimod treatment, VZV skin test antigen was injected intradermally, and clinical scores were recorded 48 hours later, as before. A history of liver disease or increased liver transaminase levels (>1.5 times the upper limit of normal) and abnormal electrocardiographic results were additional exclusion criteria for this part of the study. Serum CRP levels were measured by using a high-sensitivity assay.16 (link)
To assess compliance, ex vivo whole-blood LPS stimulation assays were performed before and 4 days after Losmapimod treatment.17 (link) Briefly, peripheral blood was cultured with LPS (0-1 mg/mL) for 24 hours (37°C in a 5% CO2 atmosphere). Levels of TNF-α and IL-6 in plasma were assessed by using the Cytometric Bead Array (CBA; BD, San Jose, Calif).