RT Journal Article
SR Electronic
T1 Safety profile and pharmacokinetics of SB010, an inhaled GATA-3-specific DNAzyme, in phase I clinical trials in healthy and asthmatic subjects
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 4858
VO 42
IS Suppl 57
A1 Ursula Homburg
A1 Agnieszka Turowska
A1 Jens Kuhlmann
A1 Anke Müller
A1 Jonas Renz
A1 Joachim Bille
A1 Harald Renz
A1 Holger Garn
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/4858.abstract
AB SB010 (a solution of the human GATA-3-specific DNAzyme hgd40) has been developed as a treatment for Th2-driven asthma. DNAzymes are single-stranded catalytic DNA molecules that bind and cleave target mRNAs. Aim of these trials was to investigate safety, tolerability and pharmacokinetics of orally inhaled SB010 in healthy subjects and asthmatic patients. We performed 3 Phase I trials: single and multiple applications in healthy subjects (trials 1, 2) and single application in stable allergic asthma patients with airway hyperresponsiveness (trial 3). All trials were performed as randomized, double-blind, placebo-controlled, parallel group (per dose level) dose-escalation trials in male subjects. SB010 was applied as nebulized solution in 6 dose levels (0.4 – 40 mg trial 1) or in 3 dose levels (5 – 20 mg trials 2+3). Adverse events (AE), vital signs, clinical chemistry, hematology, urinalysis, ECG, pulmonary function testing and overall tolerability were assessed in 108 subjects. Plasma concentrations were analyzed using a hybridization ELISA. AEs were of minor clinical relevance and fully reversible during the trials. Maximum plasma concentrations of hgd40 were detected within the highest dose groups: 1 hour after single and multiple administration in healthy subjects (29.2±20.6 ng/mL, 10.0±14.5 ng/mL); 0.75 h after single application in asthmatic patients (14.0±16.6 ng/mL), hgd40 was no longer detectable 12 h after administration. Overall, inhaled SB010 was well tolerated after single or multiple inhalation in healthy subjects or single inhalation in patients. Based on these results SB010 is currently evaluated in Phase IIa clinical trials.