Zinc Citrate Clinical Data Support Category I Efficacy - Colgate

Data from a double-blind, stratified, six-month clinical study on the efficacy of zinc citrate in reducing plaque and gingivitis supports Category I classification of the ingredient, Colgate-Palmolive states.

The Colgate brand marketer submitted the study results and accompanying protocol to satisfy questions regarding the efficacy of zinc citrate raised by FDA advisors in 1998.

Data from the study indicate a zinc citrate-containing dentifrice demonstrated "statistically significant reductions in both plaque and gingivitis" compared to placebo at both three and six months, Colgate says.

The research was executed in accordance with American Dental Association guidelines published in 1986 and revised in 1994, Colgate notes.

Conducted from April 1996 to October 1996 by Craig Williams, McWill Research Labs, and a team of researchers from Colgate-Palmolive's Clinical Dental Research Department, the study enrolled 113 men and women into two treatment groups balanced by baseline Quigley-Hein Plaque Index and Loe-Silness Gingival Index scores.

One group was given a dentifrice containing 2% zinc citrate and .76% sodium monofluorophosphate in a silica base, while the other arm received a control dentifrice containing only the .76% sodium monofluorophosphate.

Participants were instructed to brush their teeth twice daily for one minute. Tests for supragingival plaque and gingivitis were performed after three and six months.

Of the original 113 enrollees, 106 completed three months of the study and 99 finished the full six-month course. No adverse events were recorded "on the oral hard or soft tissues," the researchers note.

After three months, "whole-mouth" data showed the Plaque Index for the zinc citrate arm to be 1.88 compared to 2.20 for the placebo group, yielding a "statistically significant 14.6% plaque reduction" in the treatment arm.

A 34% reduction in the "proportion of sites with high levels of plaque accumulation" was observed in the zinc citrate group.

The Gingival Index was 1.08 and 1.26 for the zinc citrate and control groups, respectively, leading to a 14.3% gingivitis reduction in the zinc citrate arm, while a 50.5% reduction in bleeding was observed in the treatment group via the Gingivitis Severity Index.

Slightly improved "whole-mouth" results were observed after six months. Subjects in the zinc citrate group saw a 25.3% decrease in plaque and an 18.8% reduction in gingivitis, as well as a "66.7% reduction in the proportion of sites with the most severe levels of gingivitis (i.e., bleeding sites)," the researchers state.

Greater reductions in both plaque and gingivitis were observed after six months in the interproximal, lingual and posterior sites.

In summary, the results of the study "support the conclusion that a dentifrice containing 2% zinc citrate and .76% sodium monofluorophosphate in a silica base is clinically efficacious for the control of supragingival plaque and gingivitis," the researchers conclude.

Colgate's submission of the data comes almost exactly two years after the FDA Dental Plaque Subcommittee issued its draft report on oral care ingredients that would be covered under an OTC monograph for products that reduce or prevent dental plaque and gingivitis.

The sub-panel of the Nonprescription Drugs Advisory Committee reviewed zinc citrate and 15 other oral care ingredients and combinations at a meeting Dec. 2-3, 1998 (¹ (Also see "Dental Plaque Subcmte. Draft Needs Further Scientific Data - NDMA/CTFA" - Pink Sheet, 7 Dec, 1998.) and ² (Also see "Stannous Fluoride "Mild" Staining Characterization Sought In Plaque Report" - Pink Sheet, 14 Dec, 1998.)).

In its draft report, the panel deemed zinc citrate Category I (safe and effective) for safety and Category III (data insufficient) for efficacy.

The panel determined efficacy data from five short-term clinical studies, two six-month trials and a three-year trial were inconclusive due to inadequate background information, design flaws and problematic clinical endpoints. Colgate suggests the newly submitted data addresses these concerns.