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Background: Our research group has recently reported that exogenously applied histatins can inhibit plaque accumulation and gingival inflammation in a preclinical canine model (Paquette et al. 1997)., Objectives: The aims of the present double-blinded, randomized, controlled clinical trial were to evaluate the safety and toxicity of three histatin (P-113) concentrations in gel formulations, and to assess potential clinical benefit on the development of gingivitis (partial mouth design)., Material and Methods: One hundred and six healthy subjects were recruited and brought to optimal gingival health (GI < 0.5) prior to treatment initiation. At baseline, eligible subjects were randomized for one of the following treatments: (1) placebo; (2) 0.0625% P-113; (3) 0.125% P-113; and (4) 0.375% P-113. Patients self-applied gels twice daily for 29 days to the maxillary right quadrant with the use of customized stents. In addition, patients deferred all oral hygiene procedures within this quadrant for the duration of the treatment period. Safety was assessed in terms of physical and oral examinations, clinical laboratory testing and recording of adverse events. Clinical indices were measured weekly and included gingival index (GI), plaque index (PI) and %BOP., Results: All study formulations were well tolerated by patients, and no differences in adverse event occurrences were noted among treatment groups, including taste alteration or staining. For the intent-to-treat population, significantly smaller %BOP changes were noted in subjects treated with 0.0625, 0.125 and 0.375% P-113 gels (17.4, 18.18 and 17.9%, respectively) versus placebo (28.0%) (p < 0.05) at day 29. When groups were compared in terms of per cent responders (change in %BOP < 15 or < 20%), P-113 treatment groups exhibited a higher frequency of response, especially for the 0.0625 and 0.125% P-113 formulations (p < 0.05). Although no statistically significant intergroup differences were noted for changes in GI or PI among all subjects (intent-to-treat population), significantly smaller changes in PI at day 22 were observed among compliant individuals (defined as subjects using > 60% of the target gel mass) administering P-113 gels as compared with compliant placebo subjects (p < 0.05)., Conclusions: These data indicate safety and tolerance of P-113 gels for topical oral use in human subjects. These data also suggest that P-113 gels administered twice daily may reduce experimental gingivitis as measured with bleeding on probing in humans.

Objective: P-113, a 12 amino acid histatin-based peptide, was evaluated in a mouthrinse formulation for safety and efficacy in a phase 2 multi-center clinical study., Method: 294 healthy subjects abstained from oral hygiene procedures and self-administered either 0.01% P-113, 0.03% P-113 or placebo mouthrinse formulations twice daily over a 4-week treatment period. During this time, the safety, anti-gingivitis, and anti-plaque effects of P-113 were evaluated., Results: There was a significant reduction in the change from baseline to Day 22 in bleeding on probing in the 0.01% P-113 treatment group of the intent to treat population (p=0.049). Non-significant trends in the reduction of the other parameters were observed in this population (p> or =0.159). A sub-group of subjects which developed significant levels of disease within the four-week timeframe of the study was identified based on baseline gingival index scores > or =0.75. Significant findings were observed for bleeding on probing, gingival index and plaque index within this population (p<0.05). There were no treatment-related adverse events, and there were no adverse shifts in supragingival microflora during the study. Significant amounts of the peptide were retained in the oral cavity following rinsing., Conclusion: These data suggest that P-113 mouthrinse is safe and reduces the development of gingival bleeding, gingivitis and plaque in the human experimental gingivitis model.

Objective: P-113, a 12 amino acid histatin-based peptide, was evaluated in a mouthrinse formulation for safety, prevention of the development of experimental gingivitis, and for its effects on periodontal flora., Method: 159 periodontally healthy subjects abstained from oral hygiene procedures and self-administered either 0.005%, 0.01%, 0.05% P-113 or placebo mouthrinse formulations twice daily over a four week treatment period. During this time, the safety, anti-plaque, and anti-gingivitis effects of P-113 were evaluated., Results: There was a significant reduction in plaque (p=0.046) and a reduction in gingivitis (p=0.086) for subjects using 0.01% P-113 mouthrinse. Significantly more subjects in the 0.01% and 0.05% treatment groups showed a small increase in plaque index of <0.25 as compared to the placebo group (p<0.05). Similar trends were noted for changes in the % of sites with bleeding on probing in the 0.01% P-113 group. There were no treatment-related adverse events, and there were no adverse shifts in supragingival microflora during the study., Conclusion: These data suggest that P-113 mouthrinse is safe and reduces plaque, gingivitis and gingival bleeding in the human experimental gingivitis model.