Single-Dose Intraventricular Nimodipine Microparticles Versus Oral Nimodipine for Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- EG-1962 is a sustained release formulation of nimodipine administered via external ventricular drain in patients with aneurysmal subarachnoid hemorrhage. A randomized, open-label, phase 1/2a, dose-escalation study provided impetus for this study to evaluate efficacy and safety of a single intraventricular 600 mg dose of EG-1962 to patients with aneurysmal subarachnoid hemorrhage, compared with standard of care oral nimodipine. Methods- Subjects were World Federation of Neurological Surgeons grades 2-4, modified Fisher grades 2-4 and had an external ventricular drain inserted as part of standard of care. The primary end point was the proportion of subjects with favorable outcome at day 90 after aneurysmal subarachnoid hemorrhage (extended Glasgow outcome scale 6-8). The proportion of subjects with favorable outcome at day 90 on the Montreal cognitive assessment, as well as the incidence of delayed cerebral ischemia and infarction, use of rescue therapy and safety were evaluated. Results- The study was halted by the independent data monitoring board after planned interim analysis of 210 subjects (289 randomized) with day 90 outcome found the study was unlikely to achieve its primary end point. After day 90 follow-up of all subjects, the proportion with favorable outcome on the extended Glasgow outcome scale was 45% (65/144) in the EG-1962 and 42% (62/145) in the placebo group (risk ratio, 1.01 [95% CI, 0.83-1.22], P=0.95). Consistent with its mechanism of action, EG-1962 significantly reduced vasospasm (50% [69/138] EG-1962 versus 63% [91/144], P=0.025) and hypotension (7% [9/138] versus 10% [14/144]). Analysis of prespecified subject strata suggested potential efficacy in World Federation of Neurological Surgeons 3-4 subjects (46% [32/69] EG-1962 versus 32% [24/75] placebo, odds ratio, 1.22 [95% CI, 0.94-1.58], P=0.13). No safety concerns were identified that halted the study or that preclude further development. Conclusions- There was no significant increase in favorable outcome for EG-1962 compared with standard of care in the overall study population. The safety profile was acceptable. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02790632.

Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult Volunteers.

Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial ATP synthase. Bedaquiline has been used to effectively treat tuberculosis (TB) caused by drug-susceptible and drug-resistant Mycobacterium tuberculosis Rifamycins are a cornerstone of combination drug regimens for the treatment of TB. This phase 1, open-label, randomized, controlled trial evaluated the effect of steady-state dosing of rifabutin or rifampin on the safety, tolerability, and pharmacokinetics of bedaquiline given as a single dose. Thirty-three healthy subjects were enrolled to receive a 400-mg single oral dose of bedaquiline at two time points, on study days 1 and 29. Subjects were randomly assigned to once daily oral doses of rifabutin (300 mg/day, n = 17) or rifampin (600 mg/day, n = 16) during period 2 from days 20 to 41. Serial blood sampling for bedaquiline measurement occurred on days 1 and 29 through 336 h after bedaquiline administration. The day 29 bedaquiline pharmacokinetic parameter estimates were compared to the corresponding day 1 estimates for each rifamycin group. Steady-state rifampin reduced bedaquiline AUC0-336 approximately 45%, from 47.69 h·µg/ml in period 1 to 26.33 h·µg/ml in period 2. Bedaquiline apparent clearance accelerated 24% in rifampin-treated subjects from 6.59 liters/h in period 1 to 8.19 liters/h in period 2. Steady-state rifabutin resulted in little quantitative impact on bedaquiline exposure but was associated with grade 3 and 4 adverse events before and after the day 29 bedaquiline dose. Dosage adjustments may therefore be necessary to ensure that bedaquiline plasma concentrations reach therapeutic levels safely when combining bedaquiline and rifamycins in TB treatment regimens. (This single-site, randomized, open-label, prospective study in healthy adult volunteers was registered at Clinicaltrials.gov under registration no. NCT01341184.).

An induced extrinsic tooth stain prevention model to investigate whitening potential of sugar-free chewing gums.

PURPOSE: To establish an accelerated clinical test method to evaluate the effectiveness of sugar-free gums in prevention of the formation of extrinsic stains when chewed over a 2-week period in conjunction with daily tooth brushing. A secondary objective was to compare three methods for measuring extrinsic stain. METHODS: 25 healthy adult volunteers were enrolled in a single center, examiner blind, randomized 4-way crossover clinical study. Starting with a stain-free baseline, subjects rinsed five times daily with freshly brewed black tea, followed either by chewing one of three different gums for 12 minutes or not chewing (negative control). Extrinsic stain was measured at 1 and 2 weeks by modified Lobene Stain Index (MLSI), digital imaging, and a Vita EasyShade spectrophotometer. RESULTS: At 2 weeks, MLSI scores showed a statistically significant mean reduction of 43% or greater versus no-gum control for all three gum treatments. Digital image analysis and Vita EasyShade measurement showed reductions of yellowness (measured by difference in ∆b* values between the three gums and the non-gum control treatment) ranging from 0.28 to 0.34 and 3.52 to 4.18 Δb* units, respectively, for subjects using the chewing gums versus no-gum control (P< 0.05) after 2 weeks. This clinical study demonstrated that sugar-free gum can effectively reduce new stain formation along with daily tooth brushing in as little as 2 weeks when used in conjunction with tea rinsing to help promote more rapid stain formation. All three test methods confirmed the results, albeit with different levels of statistical significance. A minor modification of gum base polymer, or change of flavors, did not significantly impact the prevention of new stain formation. CLINICAL SIGNIFICANCE: Regular consumption of sugar-free chewing gum helps prevent extrinsic dental stain accumulation and provides a simple and enjoyable means for consumers to maintain their natural tooth color.

Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn.

This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific.

A 6-month clinical investigation of custom tray application of peroxide gel with or without doxycycline as adjuncts to scaling and root planing for treatment of periodontitis.

PURPOSE: To evaluate the 6-month clinical effects of one scaling and root planing (SRP) procedure alone or combined with local administration of hydrogen peroxide gel (with or without inclusion of doxycycline for 2 weeks) using periodontal medicament carriers in the form of customized prescription trays for treatment of subjects with chronic periodontitis. METHODS: Using a randomized controlled design, 61 subjects with moderate to advanced periodontitis were assigned to three parallel treatment groups: 1) SRP combined with prescription-tray (Perio Tray) application of 1.7% hydrogen peroxide gel (Perio Gel) and, for the first 2 weeks, doxycycline, 2) SRP combined with prescription-tray application of peroxide gel, and 3) SRP alone. All subjects brushed twice daily with standard dentifrice and toothbrush for a 4-week acclimation phase, and continued this regimen throughout the 6-month treatment phase. Pocket probing depth (PPD) and bleeding index (BI) were assessed on natural and restored sites at baseline and after 2, 5, 13, and 26 weeks. SRP was performed 3 weeks after baseline. Clinical variables were compared by ANCOVA and paired t-tests after each treatment interval, analyzing natural and restored sites separately. RESULTS: 57 subjects completed the trial. Analysis of pockets > 5 mm at baseline showed that mean PPD for both test groups significantly decreased from baseline approximately 0.50 mm prior to SRP. Two weeks following SRP, mean PPD significantly decreased from baseline by > 0.90 mm for both test groups and 0.29 mm for the control. By 26 weeks, mean PPD decreased > 1.10 mm for both test groups compared to 0.38 mm for the SRP-only control (P < 0.001 for test versus control at all post-SRP comparisons). Analysis of pockets ≤ 5 mm at baseline showed the same relationship between groups (P < 0.001 for test versus control). Mean BI dropped significantly only for test groups before SRP, and the tray/peroxide-doxycycline group was significantly different from the control (P = 0.033). Two weeks post-SRP, mean BI reductions for test groups were significantly greater than the control, and remained so for most comparisons. For restored sites, mean PPDs of both test groups were significantly better (P < 0.05) than the control for all post-baseline comparisons.

Crossover clinical investigation of a whitening chewing gum for inhibiting dental stain formation in conjunction with tooth brushing.

OBJECTIVE: The purpose of this clinical investigation was to evaluate the effectiveness of a marketed whitening chewing gum compared to a no-gum control in preventing the formation of extrinsic stains on the teeth of stain-forming subjects when chewed over a 12-week period of regular unsupervised use in conjunction with daily tooth brushing. METHODS: This was a single-center, examiner-blind, randomized, 12-week crossover clinical trial. Stain-forming (after smoking or drinking coffee or tea) adults, starting with a stain-free baseline, either chewed the test gum (Orbit White) unsupervised four times per day, 15 minutes/chew, or used no gum along with daily brushing with a commercially available toothbrush and dentifrice for 12 weeks. At the crossover, all procedures were repeated with subjects assigned the opposite treatment. Extrinsic stain was measured at six and 12 weeks by both the Lobene Stain Index (LSI) and the Modified Lobene Stain Index (MLSI) using separate experienced examiners. RESULTS: After 12 weeks, LSI stain scores showed a significant 25% reduction (p = 0.0008) in new stain formation for subjects using the test chewing gum along with tooth brushing versus tooth brushing alone (no-gum control). The corresponding MLSI stain scores demonstrated a 36% reduction (p < 0.0001) in the formation of extrinsic stain on the teeth. CONCLUSION: The overall findings of this clinical study demonstrated that regular use of Orbit White chewing gum, soon after smoking or drinking coffee or tea, will supplement daily tooth brushing in preventing unsightly stains from forming on the anterior teeth compared to brushing alone.

Effectiveness of a calcium sodium phosphosilicate-containing prophylaxis paste in reducing dentine hypersensitivity immediately and 4 weeks after a single application: a double-blind randomized controlled trial.

AIMS: The aim of this single-site, randomized, controlled, double-blind, 3-arm parallel study was to determine the effectiveness of a prophylaxis paste containing 15% calcium sodium phosphosilicate (CSPS; NovaMin(®) ) with and without fluoride in reducing dentine hypersensitivity immediately after a single application and 28 days following dental scaling and root planing. MATERIALS & METHODS: Overall, 151 subjects were enrolled in this study. All subjects received a scaling and root planing procedure followed by a final prophylaxis step using one of three different prophylaxis pastes: Test-A (15% NovaMin(®) and NaF), Test-B (15% NovaMin(®) ) and a control. Dentine hypersensitivity was assessed by tactile stimulus (Yeaple Probe(®) ) and by air blast (Schiff scale) at baseline, immediately after and 28 days after a prophylaxis procedure. One hundred and forty-nine subjects completed the study. RESULTS: Subjects having received the test prophylaxis pastes showed statistically lower (anova, p < 0.05) dentine hypersensitivity compared with the control group immediately after the prophylaxis procedure (Yeaple Probe(®) : Test-A = 20.9 ± 12.6, Test-B = 22.7 ± 12.9, Control=11.2 ± 3.1; Schiff score: Test-A = 1.1 ± 0.6, Test-B = 1.1 ± 0.6, Control = 2.0 ± 0.7) and after 28 days (Yeaple probe: Test-A = 21.5 ± 11.9, Test-B = 20.6 ± 11.3, Control = 11.8 ± 6.0; Schiff score: Test-A = 1.0 ± 0.6, Test-B = 1.0 ± 0.6, Control = 2.0 ± 0.7). CONCLUSIONS: In conclusion, the single application of both fluoridated and non-fluoridated prophylaxis pastes containing 15% CSPS (NovaMin(®) ) provided a significant reduction of dentine hypersensitivity up to at least 28 days.

Custom tray application of peroxide gel as an adjunct to scaling and root planing in the treatment of periodontitis: results of a randomized controlled trial after six months.

OBJECTIVE: Scaling and root planing (SRP) is the primary non-surgical treatment for periodontitis, but its effectiveness is limited. Consequently, various adjunctive therapies have been investigated to improve clinical outcome. This study evaluated the clinical effects of one SRP procedure alone or combined with local administration of hydrogen peroxide gel using customized trays for the treatment of subjects with chronic periodontitis over a period of six months. METHODS: An examiner-blind clinical trial was conducted among 30 subjects with moderate to advanced periodontitis who were randomized to SRP alone or SRP combined with prescription custom-tray application (Perio Tray) of 1.7% hydrogen peroxide gel (Perio Gel) for a period of three months, then extended to six months. Following impressions for the test group, all subjects brushed twice daily with a regular dentifrice and toothbrush for a four-week acclimation phase to standardize oral conditions (while trays were fabricated) prior to initiating the treatment phase. SRP was performed three weeks after baseline, and clinical assessments, i.e., pocket probing depth (PPD) and bleeding index (BI), were conducted at baseline and after two, five, 13, and 26 weeks of peroxide gel applications. Clinical variables were compared by ANCOVA and paired t-tests after each treatment interval. RESULTS: A total of 13 test and 15 control subjects completed the original three-month trial, of whom 10 test and 13 control subjects finished the three-month extension. After two weeks of peroxide gel use prior to SRP, mean PPD for the test group significantly decreased from baseline by 0.21 mm and mean BI significantly dropped by 0.14; clinical parameters for the control group were unchanged. Two weeks following SRP, mean PPD significantly decreased from baseline by 0.65 mm for the test group and 0.17 mm for the control; mean BI significantly dropped by 0.17 for the test group and 0.05 for the control. Ten weeks following SRP, mean PPD decreases were 0.77 mm for the test group and 0.13 mm for the control, and mean BI reductions were 0.14 for the test group and 0.00 for the control. For subjects who completed the three-month extension (i.e., 23 weeks post-SRP), mean PPD decreases were 0.72 mm for the test group and 0.13 mm for the control, and mean BI reductions were 0.05 for the test group and 0.01 for the control. Analysis of deeper pockets (i.e., > 5 mm at baseline) showed the same relationship for PPD, but with larger differences between groups. For example, after two weeks of peroxide gel use prior to SRP, mean PPD decreased by 0.48 mm for the test group compared to 0.04 mm for the control. Two weeks after SRP, mean PPD decreased from baseline by 1.40 mm for the test group and 0.60 mm for the control, and 10 weeks after SRP by 1.57 mm for the test group and 0.58 mm for the control. After the extension (i.e., 23 weeks post-SRP), mean PPD changed from baseline by 1.50 mm for the test group and 0.55 mm for the control. With the exception of BI at 23 weeks post-SRP, all reductions cited above for the test group were statistically significantly different from the control group for both PPD and BI for all comparisons. CONCLUSION: When compared with SRP alone, clinical improvements in PPD (e.g., -1.0 mm for pockets > 5 mm at baseline) were maintained for up to six months after SRP with adjunctive use of 1.7% hydrogen peroxide gel, locally administered using prescription customized trays in the treatment of subjects with moderate to advanced periodontitis.

NUPRO sensodyne prophylaxis paste with NovaMin for the treatment of dentin hypersensitivity: a 4-week clinical study.

PURPOSE: The primary objective of this study was to compare the effectiveness of NUPRO Sensodyne Prophylaxis Paste with NovaMin, with and without fluoride, to a standard prophylaxis paste without fluoride (control) in reducing dentin hypersensitivity immediately after a single application following dental scaling and root planing. The secondary objective was to compare the duration of sensitivity relief up to 28 days after a single application of the NUPRO pastes with NovaMin compared to the control paste. METHODS: This was a randomized, single-center, controlled, three-treatment, parallel-group study conducted at Salus Research in Fort Wayne, Indiana. Male and female subjects who met all inclusion/exclusion criteria and had two non-adjacent sensitive teeth based on tactile (Yeaple probe) and air blast assessments, were enrolled in the study. At baseline, tactile and air blast stimuli were administered and subjects were stratified according to their baseline air blast (Schiff) scores into one of three treatment groups: Group A (NovaMin without fluoride), Group B (NovaMin with fluoride) or Group C (NUPRO classic prophylaxis paste without fluoride). Subjects were then assessed post-treatment and at a 28-day follow-up using tactile and air blast methods. RESULTS: A total of 139 patients completed the study. Subjects having received the NovaMin containing prophylaxis pastes (Groups A and B) showed statistically lower (ANOVA, P< 0.05) dentin hypersensitivity compared to the control group immediately after the prophylaxis procedure. Group A tactile improvements were 86% immediate, and 88% after 28 days; air blast improvements were 49% immediate, and 50% after 28 days. Group B tactile improvements were 67% immediate, and 65% after 28 days; air blast improvements were 43% immediate, and 34% after 28 days. Group C experienced little improvement in tactile and air blast scores, 9% and 4% respectively, immediately following treatment, and 10% and 1% respectively after 28 days. At both time points, the reduction in sensitivity was meaningful and significantly better than in the group receiving a standard prophylaxis paste as the comparator (P< 0.05). Both NovaMin pastes were effective and there was no statistical difference between the pastes with and without fluoride. There were no adverse events reported during the course of this study.

Custom tray application of peroxide gel as an adjunct to scaling and root planing in the treatment of periodontitis: a randomized, controlled three-month clinical trial.

OBJECTIVE: Periodontitis is an inflammatory condition of the supporting dental tissues that is normally treated by mechanical removal of the subgingival biofilm. This mechanical treatment, generally known as scaling and root planing (SRP), is not entirely effective, and various adjunctive therapies have been investigated to improve the clinical outcome. This study evaluated the clinical effects of SRP alone or combined with local administration of hydrogen peroxide gel using customized trays in the treatment of subjects with chronic periodontitis. METHODS: An examiner-blind clinical trial was conducted among 30 subjects with moderate to advanced periodontitis, who were randomized to SRP alone or SRP combined with a prescription custom-tray application (Perio Tray) of 1.7% hydrogen peroxide gel (Perio Gel) for a period of three months. Following impressions for the test group, all subjects brushed twice daily with a regular dentifrice and toothbrush for a four-week acclimation phase to standardize oral conditions (while trays were fabricated) prior to initiating the treatment phase. Clinical assessments, i.e., pocket probing depth (PPD) and bleeding index (BI), were conducted at baseline and after two, five, and 13 weeks of peroxide applications; SRP was performed three weeks after baseline. Clinical variables were compared by ANOVA and paired t-tests after each treatment interval. RESULTS: A total of 13 test and 15 control subjects completed the study. After two weeks of peroxide gel use prior to SRP, mean whole-mouth PPD was unchanged for the control group, but significantly decreased 0.21 mm in the test group. Two weeks following SRP, mean PPD decreased from baseline by 0.17 mm for the control group and 0.65 mm for the test group. Ten weeks following SRP, mean PPD decreases were 0.13 mm for the control group and 0.77 mm for the test group. After two weeks of peroxide use prior to SRP, mean whole-mouth BI decreased 0.03 (from 15% to 12%) for the control and 0.14 (from 23% to 9%) for the test group. Two weeks after SRP, the mean whole-mouth BI score decreased 0.05 from baseline (15% to 10%) for the control and 0.17 (23% to 6%) for the test group. Ten weeks after SRP, there was no change from baseline for the control group, but BI was 0.14 lower (23% to 9%) for the test group. Further analysis showed the same statistical relationship between groups for PPD assessments of deeper pockets. For pockets > or =6 mm at baseline, mean PPD decreased by 0.04 mm for the control compared to 0.48 mm for the test group after two weeks of peroxide gel use and prior to SRP. Two weeks after SRP, mean PPD decreased from baseline by 0.60 mm for the control and 1.40 mm for the test group, and 10 weeks after SRP by 0.58 mm for the control and 1.57 mm for the test group. All reductions cited above for the test group were statistically significantly different from the control group for both PPD and BI. CONCLUSION: The adjunctive use over three months of 1.7% hydrogen peroxide gel, locally administered using prescription customized trays in the treatment of subjects with moderate to advanced periodontitis, demonstrated statistically significant clinical improvements in pocket depths and bleeding when compared with SRP alone.

Dosing Colistimethate Every 8 h Results in Higher Plasma Concentrations of Active Colistin Than Every 12-Hourly Dosing without Increase in Nephrotoxicity: A Phase 1 Pharmacokinetics Trial in Healthy Adult Volunteers.

Despite its use for decades, pharmacokinetic (PK) and safety studies on colistin are limited. We conducted a phase l, open-label trial to evaluate the safety and PK of multiple doses of intravenous (IV) and aerosolized colistimethate sodium (CMS) administered separately and in combination. In total, 31 healthy adults were enrolled into three cohorts of 9, 10, and 12 participants, respectively. Each cohort received increasing doses of CMS over three dosing periods as follows: Period 1 (IV only), 2.5 mg/kg every 12 h (q12h) to 3.3 mg/kg every 8 h (q8h); Period 2 (aerosolized only), 75 mg 2-4 doses, and Period 3 (combined IV aerosolized), in which was Periods 1 and 2 combined. Safety assessments, serum and lung concentrations of colistin analytes (colistin A, colistin B, CMS A, and CMS B), and kidney biomarkers were measured at specified time points. Increasing the CMS dose from 2.5 mg/kg q12h to q8h resulted in a 33% increase in serum colistin A concentrations from 3.9 µg/mL to 5.3 µg/mL-well above the accepted target of 2 µg/mL for 6 h after dosing, without evidence of nephrotoxicity. However, there was an increase in neurotoxicity, primarily perioral and lingual paresthesias, and self-limited ataxia. IV administration did not increase the lung concentrations of colistin.

Comparative investigation of a dentifrice containing triclosan/copolymer/sodium fluoride and specially-designed silica and a dentifrice containing 0.243% sodium fluoride in a silica base for the control of established supra-gingival plaque and gingivitis: a 6-month clinical study.

PURPOSE: To investigate the efficacy of a dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, 0.243% sodium fluoride, and specially-designed silica in controlling established dental plaque and gingivitis. METHODS: Qualifying adult male and female subjects from the West Palm Beach, Florida area were randomly assigned into one of two treatment groups: (1) a dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, 0.243% sodium fluoride, and specially-designed silica (Test Dentifrice); and (2) a dentifrice containing 0.243% sodium fluoride in a silica base (Negative Control Dentifrice). All subjects received an oral soft and hard tissue examination, baseline plaque and gingivitis were assessed, and subjects were dispensed their assigned dentifrice product along with a soft-bristled adult toothbrush for home use. Subjects were instructed to brush their teeth for 1 minute, twice daily (morning and evening), using only the dentifrice provided. Examinations for plaque and gingivitis, and oral soft and hard tissue assessments were repeated after 3 and 6 months of product use. RESULTS: 115 subjects complied with the protocol, and completed the 6-month examination. After 6 months of product use, subjects assigned to the Test Dentifrice group exhibited statistically significant reductions from baseline with respect to Plaque Index, Plaque Severity Index, Gingival Index, and Gingivitis Severity Index scores; and subjects assigned to the Negative Control Dentifrice group exhibited statistically significant reductions from baseline with respect to Gingival Index scores only. Relative to the Negative Control Dentifrice group, the Test Dentifrice group exhibited an 18.8% reduction in Plaque Index; a 50% reduction in Plaque Severity Index; a 19.6% reduction in Gingival Index; and a 60% reduction in Gingivitis Severity Index after 6 months, all of which were statistically significant.

Characterization of Polybacterial versus Monobacterial Conjunctivitis Infections in Pediatric Subjects Across Multiple Studies and Microbiological Outcomes with Besifloxacin Ophthalmic Suspension 0.6.

INTRODUCTION: The choice of empiric therapy for bacterial conjunctivitis should be guided by an awareness of typical causative pathogen distributions. Bacterial conjunctivitis can be polybacterial, although pediatric-specific data are lacking. METHODS: This was a post-hoc analysis of data in pediatric subjects (1-17 years) from five bacterial conjunctivitis trials evaluating besifloxacin ophthalmic solution 0.6%. RESULTS: Of the 730 pediatric subjects with culture-confirmed conjunctivitis, nearly one-fourth (23.6%) had polybacterial infections and three-fourths (76.4%) had monobacterial infections at baseline. In both polybacterial and monobacterial infections, the most prevalent organisms were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus mitis/S. mitis group. In polybacterial versus monobacterial infections, S. mitis/S. mitis group (8.7% vs 4.3%; P=0.032) and Moraxella catarrhalis (4.7% vs 0.5%; P<0.001) were identified more frequently, whereas S. pneumoniae (14.0% vs 28.1%; P<0.001) was identified less frequently, as the dominant infecting species. MICs for individual species were similar for tested antibiotics regardless of polybacterial or monobacterial infection, except Staphylococcus epidermidis for which fluoroquinolone MICs were ≥3 dilutions higher for isolates of this species sourced from polybacterial compared to monobacterial infections. Treatment with besifloxacin resulted in microbial eradication in 79.1% of polybacterial and 92.3% of monobacterial infections (P≤0.005 vs vehicle). DISCUSSION: One in four pediatric bacterial conjunctivitis infections is polybacterial, highlighting the need for a broad-spectrum antibiotic when choosing empiric therapy.

A comparison of the efficacy of a triclosan/copolymer/sodium fluoride dentifrice, a stannous fluoride/sodium hexametaphosphate/zinc lactate dentifrice, and a sodium fluoride dentifrice for the control of established supragingival plaque and gingivitis: a six-week clinical study.

OBJECTIVE: To compare the efficacy ofa dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, and 0.243% sodium fluoride in controlling established gingivitis and supragingival plaque to that of a commercially available dentifrice containing 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate, and a commercially available dentifrice containing 0.243% sodium fluoride. METHODS: Following a baseline examination for gingivitis and supragingival plaque, qualifying adult male and female subjects from the Mississauga, Ontario, Canada area were randomized into three dentifrice groups. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice and a soft-bristled toothbrush. Examinations for gingivitis and supragingival plaque were repeated after six weeks of product use. RESULTS: One-hundred eighty-two (182) subjects complied with the protocol and completed the study. Relative to the 0.243% sodium fluoride dentifrice group, the 0.3% triclosan/2.0% PVM/MA copolymer/0.243% sodium fluoride dentifrice group exhibited statistically significant reductions in gingival index and supragingival plaque index scores of 26.5% and 29.4%, respectively, after six weeks of product use. Similarly, relative to the 0.243% sodium fluoride dentifrice group, the 0.454% stannous fluoride/sodium hexametaphosphate/zinc lactate dentifrice group exhibited statistically significant reductions in gingival index and plaque index scores of 12.7% and 12.6%, respectively, after six weeks of product use. Further, relative to the 0.454% stannous fluoride/sodium hexametaphosphate/zinc lactate dentifrice group, the 0.3% triclosan/2.0% PVM/MA copolymer/0.243% sodium fluoride dentifrice group exhibited statistically significant reductions in gingival index and plaque index scores of 15.8% and 19.2%, respectively. CONCLUSION: The overall results of this double-blind clinical study support the conclusion that a dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, and 0.243% sodium fluoride is efficacious for the control of established gingivitis and supragingival plaque, and that it provides a greater level of efficacy for the control of gingivitis and supragingival plaque than does a dentifrice containing 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate.

A clinical investigation of the efficacy of three commercially available dentifrices for controlling established gingivitis and supragingival plaque.

OBJECTIVE: To assess the efficacy ofa dentifrice containing 0.3% triclosan/2.0% PVM/MA copolymer/0.243% sodium fluoride for controlling established gingivitis and supragingival plaque relative to that of a dentifrice containing 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate, and a dentifrice containing 0.243% sodium fluoride as a negative control. METHODS: Following a baseline examination for gingivitis and supragingival plaque, qualifying adult male and female subjects from the Piscataway, NJ, USA area were randomized into three dentifrice groups. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice and a soft-bristled toothbrush. Examinations for gingivitis and supragingival plaque were repeated after six weeks of product use. RESULTS: One-hundred and seventy-one (171) subjects complied with the protocol and completed the study. Relative to the group using the dentifrice with 0.243% sodium fluoride alone, the 0.3% triclosan/2.0% PVM/MA copolymer/0.243% sodium fluoride group exhibited statistically significant reductions in gingival index and supragingival plaque index scores of 25.3% and 33.0%, respectively, after six weeks of product use. Similarly, relative to the group using the 0.243% sodium fluoride dentifrice, the 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate dentifrice group exhibited statistically significant reductions in gingival index and plaque index scores of 8.1% and 14.1% after six weeks of product use. Further, relative to the 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate dentifrice group, the 0.3% triclosan/2.0% PVM/MA copolymer/0.243% sodium fluoride dentifrice group exhibited statistically significant reductions in gingival index and plaque index scores of 18.7% and 22%, respectively. CONCLUSION: The overall results of this double-blind clinical study support the conclusion that a dentifrice containing 0.3% triclosan/2.0% PVM/MA copolymer/0.243% sodium fluoride is efficacious for the control of established gingivitis and supragingival plaque as compared to a regular fluoride dentifrice, and that it provides a greater level of efficacy for the control of gingivitis and supragingival plaque than does a dentifrice containing 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate.

Comparative investigation of the efficacy of triclosan/copolymer/sodium fluoride and stannous fluoride/sodium hexametaphosphate/zinc lactate dentifrices for the control of established supragingival plaque and gingivitis in a six-month clinical study.

OBJECTIVE: This double-blind clinical study, conducted at the University of Puerto Rico, San Juan, Puerto Rico, was designed to compare the efficacy of two commercially available dentifrices for the control of supragingival plaque and gingivitis. METHODS: Qualifying adult male and female subjects from the San Juan, Puerto Rico area were randomly assigned to one of two treatment groups: 1) a commercially available dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, and 0.243% sodium fluoride (Colgate Total); and 2) a commercially available dentifrice containing 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate (Crest Pro-Health). All subjects received an oral soft and hard tissue examination, and were dispensed their assigned dentifrice product, along with a soft-bristled adult toothbrush for home use. Subjects were instructed to brush their teeth for one minute, twice daily (morning and evening), using only the dentifrice provided. Examinations for supragingival plaque and gingivitis, and oral soft and hard tissue assessments were repeated after six weeks, three months, and six months of product use. RESULTS: One-hundred and nine (109) subjects complied with the protocol and completed the six-month examinations. At the six-month examination, both treatment groups exhibited statistically significant reductions from baseline with respect to supragingival plaque and gingivitis scores. Relative to the Crest Pro-Health Toothpaste group, the Colgate Total Toothpaste group exhibited statistically significant reductions in supragingival plaque index scores of 18.5%, 20.7%, and 25.8% after six weeks, three months, and six months of product use, respectively. For gingival index scores, statistically significant reductions of 20.5%, 18.9%, and 17.1% were exhibited after six weeks, three months, and six months of product use, respectively. CONCLUSION: The results of this double-blind clinical study support the conclusion that a dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, and 0.243% sodium fluoride provides a significant reduction in established supragingival plaque and gingivitis, as compared to a dentifrice containing 0.454% stannous fluoride, sodium hexametaphosphate, and zinc lactate when used over a period of six months.

Characterization of baseline polybacterial versus monobacterial infections in three randomized controlled bacterial conjunctivitis trials and microbial outcomes with besifloxacin ophthalmic suspension 0.6.

BACKGROUND/PURPOSE: To date, studies examining polymicrobial infections in ocular disease have mostly been limited to keratitis or endophthalmitis. We characterized polybacterial infections compared to monobacterial infections in prior clinical studies evaluating besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial conjunctivitis and report on associated microbiological outcomes. METHODS: In this post-hoc analysis, microbiological data for subjects with conjunctivitis due to one or more than one bacterial species in three previous studies (two vehicle-, one active-controlled) of besifloxacin were extracted. Bacterial species identified at baseline were deemed causative if their colony count equaled or exceeded species-specific prespecified threshold criteria. In subjects with polybacterial infections, the fold-increase over threshold was used to rank order the contribution of individual species. Baseline pathogens and their minimum inhibitory concentrations (MICs) for common ophthalmic antibiotics were compared by infection type, as were microbial eradication rates following treatment with besifloxacin. RESULTS: Of 1041 subjects with culture-confirmed conjunctivitis, 17% had polybacterial and 83% had monobacterial conjunctivitis at baseline. In polybacterial compared to monobacterial infections, Haemophilus influenzae and Streptococcus pneumoniae were identified less frequently as the dominant infecting species (P = 0.042 and P<0.001, respectively), whereas Streptococcus mitis/S. mitis group was identified more frequently as dominant (P<0.001). Viral coinfection was also identified more frequently in polybacterial infections (P<0.001). Staphylococcus aureus was the most common coinfecting species in polybacterial infections and the second most common dominant species in such infections. With few exceptions, MICs for individual species were comparable regardless of infection type. Clinical microbial eradication rates with besifloxacin were high regardless of infection type (P≤0.016 vs vehicle at follow-up visits). CONCLUSIONS: Approximately one in five subjects with bacterial conjunctivitis are infected with more than one bacterial species underscoring the need for a broad-spectrum antibiotic for such infections. Besifloxacin treatment resulted in robust eradication rates of these infections comparable to monobacterial infections. TRIAL REGISTRATION: NCT000622908, NCT00347932, NCT00348348.

A two-part phase 1 study to establish and compare the safety and local tolerability of two nasal formulations of XF-73 for decolonisation of Staphylococcus aureus: A previously investigated 0.5mg/g viscosified gel formulation versus a modified formulation.

OBJECTIVES: Successful decolonisation of nasal Staphylococcus aureus (SA) carriage by mupirocin is limited by increasing drug resistance. This randomised, open-label, phase 1 study compared the safety and local tolerability of two nasal formulations of XF-73, a novel porphyrinic antibacterial with rapid intrinsic activity against SA. METHODS: The study was performed in 60 healthy adults. In Part 1, eight non-SA carriers were randomised to groups of four subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel or 2.0mg/g 2% gel. In Part 2, 52 persistent SA carriers were randomised to groups of 13 subjects each and were treated with XF-73 concentrations of 0.5mg/g 2% gel, 2.0mg/g 2% gel, 0.5mg/g 4% gel or 4% viscosified placebo gel. Plasma pharmacokinetic and pharmacodynamic studies were performed. Antistaphylococcal activity was assessed as the presence/absence of SA and by quantification of colonisation using a semiquantitative scale (SA score). RESULTS: 56 subjects (8/8 from Part 1 and 48/52 from Part 2) completed the study, with 47/60 comprising the pharmacokinetic population and 48/60 the pharmacodynamic population. There was no measurable systemic absorption of XF-73. XF-73 treatment was associated with rapid reduction in SA score in all subjects. The most common treatment-emergent adverse events (TEAEs) were rhinorrhoea and nasal dryness (15.5% each in Parts 1 and 2). TEAEs were mild and resolved spontaneously. CONCLUSION: XF-73 was well tolerated with minimal side effects at doses of 0.5mg/g 2% gel and 2.0mg/g 2% gel. These findings support further development of XF-73.

Clinical investigation of the efficacy of a commercial mouthrinse containing 0.05% cetylpyridinium chloride in reducing dental plaque.

OBJECTIVE: The objective of this independent, double-blind, seven-day clinical study was to assess the efficacy of a commercially available mouthrinse containing 0.05% CPC for controlling dental plaque relative to that of a control mouthrinse without 0.05% CPC. METHODS: Adult male and female subjects from the San Juan, Puerto Rico area reported to the clinical facility, having refrained from any oral hygiene procedures for 12 hours, and from eating, drinking, and smoking for four hours, for an assessment of the oral soft and hard tissues and a baseline dental plaque evaluation. Qualifying subjects were randomly assigned into one of the two treatment groups, and were provided with their assigned mouthrinse, an adult soft-bristled toothbrush, and a commercially available fluoride toothpaste for home use. Over the seven-day period of home use, during which there were no restrictions regarding diet or smoking habits, subjects were instructed to brush their teeth for one minute twice daily (morning and evening) with the toothbrush and toothpaste supplied, to rinse their mouths with water after brushing, and then to rinse with 15 ml of their assigned mouthrinse for one minute before expectorating. The use of other oral hygiene products or procedures, such as floss or interdental stimulators, was not permitted during the study. After seven days of product use, subjects returned to the clinical facility having followed the same restrictions with respect to oral hygiene procedures, eating, and drinking as prior to the baseline examination, and the oral soft and hard tissue assessments and dental plaque evaluations were repeated. Comparisons between treatment groups with respect to baseline-adjusted Plaque Index scores at the seven-day examination were performed using Analyses of Covariance, p < or = 0.05. RESULTS: Forty-eight subjects complied with the protocol and completed the study. Results demonstrated that, after seven days of product use and 12 hours after rinsing, both the CPC mouthrinse group and the control mouthrinse group exhibited statistically significant reductions in whole-mouth Plaque Index scores (25.3% and 6.6%, respectively), in Plaque Index scores measured at interproximal sites (51.3% and 32.9%, respectively), and in Plaque Severity Index scores (43.5% and 25.4%, respectively). Relative to the control mouthrinse, the 0.05% CPC mouthrinse group exhibited statistically significant greater reductions in whole-mouth plaque scores (15.9%), in Plaque Index scores measured at interproximal sites (23%), and in Plaque Severity Index scores (17%). As the measurements were made 12 hours after final product use, the results also demonstrate that the CPC mouthrinse provides 12-hour protection against plaque accumulation in individuals with existing plaque. CONCLUSION: The overall results of this double-blind clinical study support the conclusion that after seven days of product use, a mouthrinse containing 0.05% CPC provides significantly greater efficacy for reducing dental plaque 12 hours after use, than does a control mouthrinse without 0.05% CPC.

Clinical investigation of the efficacy of a commercial mouthrinse containing 0.05% cetylpyridinium chloride in preventing dental plaque.

OBJECTIVE: The objective of this independent, double-blind, seven-day clinical study was to assess the efficacy of a commercially available mouthrinse containing 0.05% cetylpyridinium chloride (CPC) in preventing dental plaque build-up relative to that of a control mouthrinse without 0.05% CPC. METHODS: Adult male and female subjects from the São Paulo, Brazil area reported to the clinical facility, having refrained from any oral hygiene procedures for 12 hours, and from eating, drinking, and smoking for four hours, for an assessment of the oral soft and hard tissues and a baseline dental plaque evaluation. Subjects qualifying for participation received a complete dental prophylaxis. Qualifying subjects were randomly assigned into one of the two treatment groups and were provided with their assigned mouthrinse, an adult soft-bristled toothbrush, and a commercially available fluoride toothpaste for home use. Over the seven-day period of home use, during which there were no restrictions regarding diet or smoking habits, subjects were instructed to brush their teeth for one minute twice daily (morning and evening) with the toothbrush and toothpaste supplied, to rinse their mouths with water after brushing, and then to rinse with 15 ml of their assigned mouthrinse for one minute before expectorating. The use of other oral hygiene products or procedures, such as floss or interdental stimulators, was not permitted during the study. After seven days of product use, subjects returned to the clinical facility having followed the same restrictions with respect to oral hygiene procedures, eating and drinking, as prior to the baseline examination, and the oral soft and hard tissue assessments and dental plaque evaluations were repeated. RESULTS: Forty-three subjects complied with the protocol and completed the study. Results demonstrated that after seven days of product use, mean plaque levels were statistically significantly lower (p < 0.05) than the pre-prophylaxis levels for both treatment groups. The mean plaque level for the CPC mouthrinse group was 46.1% of the pre-prophylaxis plaque level, whereas the mean plaque level for the control mouthrinse group was 75.5% of the pre-prophylaxis plaque level. The results demonstrate a statistically significant reduction in plaque build-up for the CPC mouthrinse group (29.3%) as compared to the control group. CONCLUSION: The overall results from this double-blind clinical study support the conclusion that, after seven days of product use, a mouthrinse containing 0.05% CPC provides significantly greater efficacy in preventing dental plaque build-up than a control mouthrinse without 0.05% CPC. As measurements were made 12 hours after final product use, the results also demonstrate that the CPC rinse provides 12-hour protection against dental plaque build-up.