Chlorhexidine Diacetate Delivery System: Phase I Clinical Trial

Chlorhexidine diacetate (CDA) has been incorporated (2.5% by weight) into ethylene vinyl acetate (EVA) films and fabricated as mouthguards for the treatment of HIV-associated oral infections. In vitro testing indicates sustained concentrations of CDA for 21 days. Objectives: 1) To evaluate the safety of the 2.5% CDA-EVA delivery system over 21 days in medically healthy subjects with gingivitis. 2) To document the pharmacokinetic profiles of CDA in serum and saliva. Methods: Six subjects with generalized moderate plaque-induced gingivitis were recruited for this open-label, phase I trial. CDA-EVA mouthguards were fabricated to fit the maxillary arches of subjects and worn 12hrs/day for 21 days. Oral exams, adverse event reporting and pharmacokinetic monitoring (blood and saliva) were performed at Baseline, Days 1, 2, 3, 7, 14, 21 and 35. Full-mouth probing exams (pocket depth, clinical attachment level, bleeding on probing, gingival, plaque, calculus and discoloration indices) were conducted at Baseline, Days 21 and 35. Blood chemistries, hematology and urinalysis were determined at screening and Day 21. Serum and saliva samples (22 time points) were analyzed for CDA using HPLC. Results: All subjects tolerated the CDA delivery system over the 21 days with no severe adverse events or alterations in blood chemistries, hematology or urinalysis. In general, calculus, discoloration and periodontal indices decreased with treatment. An analysis of covariance indicated significant reductions in pocket depth for the maxillary arch (controlling for the mandibular) over the 21-day treatment period (p<0.05). Only 6% of serum samples had detectable CDA levels (>10ng/ml), but the maximum was 12ng/ml. Meanwhile 49% of saliva samples had detectable CDA with a maximum of 889ng/ml. Conclusions: The CDA-EVA system appears safe in humans with minimal systemic exposure. Prolonged intraoral CDA delivery may improve signs of oral infection (gingivitis). A phase II trial in HIV subjects may proceed. [Supported by DE15267-01, RR00046]