Clinical Trials Resource Center

FDA Approved Drugs » 1999
Medical Areas: Dental and Oral Health

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Atridox

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: Atrix Laboratories
Approval Status: Approved January 1999
Treatment Area: Dental/Maxillofacial Surgery

General Information

ATRIDOX is indicated for use in the treatment of chronic adult periodontitis for a gain in clinical attachment, reduction in probing depth, and reduction in bleeding on probing.

The ATRIDOX product is a subgingival controlled-release product composed of a two syringe mixing system. Syringe A contains 450 mg of the ATRIGEL® Delivery System, which is a bioabsorbable, flowable polymeric formulation composed of 36.7% poly(DL-lactide) (PLA) dissolved in 63.3% N-methyl-2-pyrrolidone (NMP). Syringe B contains doxycycline hyclate which is equivalent to 42.5 mg doxycycline. The constituted product is a pale yellow to yellow viscous liquid with a concentration of 8.5% w/w of doxycycline.

Clinical Results

In two well-controlled, multicenter, parallel-design, nine-month clinical trials, 831 patients (Study 1=411; Study 2=420) with chronic adult periodontitis characterized by a mean probing depth of 5.9 to 6.0 mm were enrolled. Subjects received one of four treatments:

  • ATRIDOX
  • Scaling and Root Planing
  • Vehicle Control
  • Oral Hygiene

Treatment was administered to sites with probing depths 5 mm or greater that bled on probing. Subjects with detectable subgingival calculus on greater than 80% of all tooth surfaces were excluded from enrollment. All subjects received a second administration of the initially randomized treatment four months after their baseline treatment. Changes in the efficacy parameters, attachment level, pocket depth, and bleeding on probing, between baseline and month 9 showed that:

  • ATRIDOX was superior to Vehicle Control and Oral Hygiene
  • ATRIDOX met the decision rule of being at least 75% as good as Scaling and Root Planing (SRP) (the standard of at least 75% as good as SRP is required for any product approved as a stand alone therapy for periodontitis).

A single-center, single-blind, randomized, clinical study in 45 subjects with periodontal disease demonstrated that a single treatment with ATRIDOX resulted in the reduction in the numbers of P. gingivalis, P. intermedia, C. rectus, F. nucleatum, Bacteroides forsythus, and E. corrodens in subgingival plaque samples. Levels of aerobic and anaerobic bacteria were also reduced after treatment with ATRIDOX. The clinical significance of these findings, however, is not known. During these studies, no overgrowth of opportunistic organisms such as Gram-negative bacilli and yeast were observed. However, as with other antibiotic preparations, ATRIDOX therapy may result in the overgrowth of nonsusceptible organisms including fungi.

Clinicians should note that the studies were of nine months duration. Additional research would be necessary to establish long term comparability to SRP.

Side Effects

ATRIDOX should not be used in patients who are hypersensitive to doxycycline or any other drug in the tetracycline class.

In clinical trials involving a total of 1436 patients, adverse experiences were monitored across treatment groups.

In the Circulatory System category, 10 subjects (1.6%) in the ATRIDOX group were reported as having unspecified essential hypertension. Only 1 subject (0.2%) in the Vehicle group, and none in the Scaling and Root Planing or Oral Hygiene groups were reported to have unspecified essential hypertension. In all cases, the event occurred anywhere from 13 to 134 days post-treatment.

There is no known association of oral administration of doxycycline with essential hypertension.

Two patients in the polymer vehicle group and none in the ATRIDOX group (0.2% for both groups combined) reported adverse events consistent with a localized allergic response.

Sex, age, race and smoking status did not appear to be correlated with adverse events.

Mechanism of Action

Doxycycline is a broad-spectrum semisynthetic tetracycyline.1 Doxycycline is bacteriostatic, inhibiting bacterial protein synthesis due to disruption of transfer RNA and messenger RNA at ribosomal sites.

In vitro testing has shown that Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, and Fusobacterium nucleatum, which are associated with periodontal disease, are susceptible to doxycycline at concentrations <6.0 µg/mL.