Listerine With Fluoride Proposed Six-Month Study To Be Reviewed By FDA

Pfizer Consumer Healthcare plans to conduct a six-month clinical study involving at least 300 subjects to determine whether adding .02% sodium fluoride to the company's Listerine mouthrinse affects the antiplaque/ antigingivitis effectiveness of the product.

The primary aim of the single-center, double-blind, parallel-group trial will be to prove the essential oil-containing mouthrinse with fluoride is both statistically significantly better than a negative control and "at least as good as" a mouthrinse without fluoride at "inhibiting the development of supragingival dental plaque and gingivitis," Pfizer states.

Participants ages 18-65 will be instructed to rinse twice daily with 20 mL of either Listerine with fluoride, Listerine without fluoride or a 5% hydroalcohol negative control, while continuing their usual oral therapy with a fluoride toothpaste.

Primary efficacy variables for the study will be mean Modified Gingival Index (MGI) and mean Plaque Index (PI) ratings at six months, while secondary measures will be mean Bleeding Index at three and six months and mean MGI and mean PI at three months.

The protocol for the proposed study was among materials submitted to FDA by Pfizer on May 30 in preparation for an OTC "feedback" meeting to be held in Rockville, Md. June 18.

The "feedback" meeting is the next step in Pfizer's lengthy efforts to amend the OTC anticaries drug products monograph to allow a mouthrinse combining essential oils and sodium fluoride. The campaign, initiated by Warner-Lambert prior to the firm's acquisition by Pfizer, would result in a cross-monograph product marketed as FreshBurst Listerine with Fluoride.

Pfizer's proposal to measure efficacy through both MGI and PI ratings appears to reflect earlier comments from FDA criticizing certain design characteristics of an experimental gingivitis study and an intraoral caries test model (IOA) study previously conducted by Pfizer/ Warner-Lambert (¹ (Also see "W-L Listerine Anticaries Rinse Gingivitis Assessment Required - FDA" - Pink Sheet, 16 Jul, 2001.), p. 14).

Results from the shorter experimental gingivitis model study and the IOA study also will be discussed at the June 18 meeting with FDA, as will Pfizer's proposed changes to the anticaries final monograph, which was first published in October 1995.

Pfizer reps at the meeting will include execs from product development, oral care technology development, oral care R&D, regulatory affairs and statistics.

The shorter gingivitis model study, which assessed the safety and efficacy of a .02% sodium fluoride and Listerine mouthrinse combination, was completed by Suru Mankodi, et al., Dental Products Testing, West Palm Beach, Fla., in September 2000.

The study found that the essential oil-containing rinse/fluoride combination produces a statistically significant reduction in gingival inflammation and plaque when compared to a negative control, according to Pfizer. The combo also was "at least as good as" the standard essential oil-containing rinse at inhibiting gingival inflammation and plaque, the firm says.

The trial involved 200 subjects who used 20 mL of either the combination rinse, the standard rinse or the negative control (5% hydroalcohol) twice a day for 30 seconds over a two-week period. The study's primary efficacy variables were mean MGI and mean PI ratings at two weeks.

In a synopsis of the study, Pfizer shows the combination achieved a reduction of 12.3% on the MGI and of 30% on the PI "relative to the negative control." Comparatively, the standard rinse produced 14.8% and 28.4% reductions on the respective tests relative to the negative control. The researchers also noted that no treatment-related adverse events were recorded during the study.

The IOA study which FDA and Pfizer will discuss at the feedback meeting was conducted by Domenick Zero, et al., Oral Health Research Institute, Indianapolis, Ind.

The study determined that rinsing with 20 mL of the combination mouthrinse for 30 seconds twice daily over a two-week period is "effective in increasing both percent surface microhardness recovery and fluoride uptake by a statistically greater amount than" identical dosing of a standard mouthrinse.

In addition, the 20 mL dose is "at least as good as" 10 mL of the combination used for 60 seconds twice daily, the regimen currently recommended in the anticaries monograph, the researchers report.