In February 2013, Glaxosmithkline (GSK) Announced a Commitment To
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In February 2013, GlaxoSmithKline (GSK) announced a commitment to further clinical transparency through the public disclosure of GSK Clinical Study Reports (CSRs) on the GSK Clinical Study Register. The following guiding principles have been applied to the disclosure: Information will be excluded in order to protect the privacy of patients and all named persons associated with the study Patient data listings will be completely removed* to protect patient privacy. Anonymized data from each patient may be made available subject to an approved research proposal. For further information, please see the Patient Level Data section of the GSK Clinical Study Register. Aggregate data will be included; with any direct reference to individual patients excluded *Complete removal of patient data listings may mean that page numbers are no longer consecutively numbered Document Name RH205051 Synopsis Type Version Document Identifier Effective Date eldo_controlled 1.0; CURRENT; Most-Recent; Effective 090032d580d18c62 Reason For Issue Synopsis Report Study Number 205051 Study Title A Study to Investigate the Ant imicrobial Activity of two Test toothpastes in a Plaque Glycolysis and Regrowth Model. Test Product(s) Test toothpaste containing 0.6% w/w zinc chloride and 0.1% w/w isopropylmethylpheno l (IPMP) and 1426ppm fluoride as sodium fluoride. Indication Ant imicrobial activity Phase Not Applicable Authors: Clinical Operations PPD , HND BioStatistics PPD , BSc, MSc Clinical Research PPD , BS Approvers: Clinical Operations PPD , PhD BioStatistics PPD , BSc, CStat Clinical Research PPD , BSc, MSc, CStat Copyright: GlaxoSmithKline. An unpublished work subject to trade secret protection. This work contains confidential and proprietary information of GlaxoSmithKline and should not be copied, circulated, or distributed to persons not employed by GlaxoSmithKline unless specifically authorized. Unauthorized disclosure of this work is expressly prohibited. Document Version:3.0,Most-Recent,Effective,CURRENT Page 1 of 209 Document Name RH205051 Synopsis Type Version Document Identifier Effective Date eldo_controlled 1.0; CURRENT; Most-Recent; Effective 090032d580d18c62 Reason For Issue Table of Contents Page 205051 SYNOPSIS 4 TABLE 9.1.1.1 SUBJECT DISPOSITION BY TREATMENT GROUP ACROSS STUDY TREATMENT PERIODS ALL SCREENED SUBJECTS 20 TABLE 9.1.1.2 SUBJECT DISPOSITION BY TREATMENT GROUP AND STUDY TREATMENT PERIOD ALL SCREENED SUBJECTS 22 TABLE 9.1.2 PROTOCOL VIOLATIONS LEADING TO EXCLUSION FROM PER PROTOCOL ANALYSIS INTENT TO TREAT POPULATION 28 TABLE 9.2.1.1 DEMOGRAPHIC AND BASELINE CHARACTERISTICS SAFETY POPULATION 29 TABLE 9.2.1.2 DEMOGRAPHIC AND BASELINE CHARACTERISTICS PER PROTOCOL POPULATION 30 TABLE 9.3.1.1 SUMMARY AND ANALYSIS OF MEASUREMENTS OF GLYCOLYSIS BY TIMEPOINT PER PROTOCOL POPULATION 31 TABLE 9.3.1.2 TREATMENT COMPARISONS OF MEASUREMENTS OF GLYCOLYSIS BY TIMEPOINT PER PROTOCOL POPULATION 35 TABLE 9.3.1.3 SUMMARY AND ANALYSIS OF AUCGLY(0-90) PER PROTOCOL POPULATION 38 TABLE 9.3.2 SUMMARY AND ANALYSIS OF AUCGLY(0-90): SUBGROUP ANALYSIS BY PRE-STUDY BASELINE PH LEVEL PER PROTOCOL POPULATION 40 TABLE 9.3.3.1 SUMMARY AND ANALYSIS OF MEASUREMENTS OF REGROWTH RATIO BY TIMEPOINT PER PROTOCOL POPULATION 44 TABLE 9.3.3.2 TREATMENT COMPARISONS OF MEASUREMENTS OF REGROWTH RATIO BY TIMEPOINT PER PROTOCOL POPULATION 48 TABLE 9.3.3.3 SUMMARY AND ANALYSIS OF AUCREGROWTH(0-90) PER PROTOCOL POPULATION 51 TABLE 9.3.4.1 SUMMARY AND ANALYSIS OF MEASUREMENTS OF LIVE:DEAD STAIN RATIO BY TIMEPOINT PER PROTOCOL POPULATION 53 TABLE 9.3.4.2 TREATMENT COMPARISONS OF MEASUREMENTS OF LIVE:DEAD STAIN RATIO BY TIMEPOINT PER PROTOCOL POPULATION 57 TABLE 9.3.4.3 SUMMARY AND ANALYSIS OF AUCLIVE:DEAD(0-90) PER PROTOCOL 60 POPULATION TABLE 9.4.2 TREATMENT EMERGENT TREATMENT RELATED ADVERSE EVENTS 73 SAFETY POPULATION TABLE 9.4.3 TREATMENT EMERGENT ADVERSE EVENTS SAFETY POPULATION 75 TABLE 9.4.4 TREATMENT EMERGENT TREATMENT RELATED ADVERSE EVENTS SAFETY POPULATION 79 TABLE 9.4.5 TREATMENT EMERGENT ADVERSE EVENTS SAFETY POPULATION 81 FIGURE 9.1 MEAN PLAQUE INCUBATION PH OVER TIME PER PROTOCOL POPULATION 86 FIGURE 9.2 MEAN REGROWTH RATIO OVER TIME PER PROTOCOL POPULATION 87 Page 2 of 209 Document Name RH205051 Synopsis Type Version Document Identifier Effective Date eldo_controlled 1.0; CURRENT; Most-Recent; Effective 090032d580d18c62 Reason For Issue FIGURE 9.3 MEAN LIVE:DEAD STAIN RATIO OVER TIME PER PROTOCOL POPULATION 88 FIGURE 9.4 MEAN CHANGE IN PLAQUE INCUBATION PH FROM PRE-TREATMENT PER PROTOCOL POPULATION 89 FIGURE 9.5 MEAN CHANGE IN REGROWTH RATIO FROM PRE-TREATMENT PER PROTOCOL POPULATION 90 FIGURE 9.6 MEAN CHANGE IN LIVE:DEAD STAIN OVER TIME PER PROTOCOL POPULATION 91 FIGURE 9.7 SCATTER PLOT OF BASELINE PH VERSUS AUCGLY(0-90) PER PROTOCOL POPULATION 92 Page 3 of 209 Document Name RH205051 Synopsis Type Version Document Identifier Effective Date eldo_controlled 1.0; CURRENT; Most-Recent; Effective 090032d580d18c62 Reason For Issue Study: 205051 Synopsis Report Name of Company: GlaxoSmithKline Consumer Healthcare Name of Finished Product: Toothpaste containing 0.6% w/w zinc chloride and 0.1% w/w IPMP and 1426ppm fluoride as sodium Name of Active Ingredient: Zinc chlor ide, Isopropylmethylphenol, sodium fluoride Title of Study: A Study to Investigate the Antimicrobial Activity of two Test Toothpastes in a Plaque Glycolysis and Regrowth Model. Investigator: Dr. David Payne, BDS Study centre: Intertek - Brindley Road, Manchester, UK Publication (reference): Not Applicable Study period: First Enrolment: 09 Nov 2015 Last Completed: 11 Dec 2015 Clinical Phase: Not Applicable Objectives: Primary Objective To evaluate and compare the ability of a test toothpaste containing 0.6% zinc chloride and 0.1% isopropylmethylphenol (IPMP) to inhibit plaque glycolysis compared to a non-sodium lauryl sulphate (SLS) containing toothpaste. Secondary Objectives To evaluate and compare the ability of a test toothpaste containing 0.6% zinc chloride and 0.1% IPMP to inhibit plaque viability by regrowth as compared to a non-SLS containing toothpaste. To evaluate and compare the ability of a test toothpaste containing 0.6% zinc chloride and 0.1% IPMP to inhibit plaque viability by live:dead staining compared to a non- SLS containing toothpaste. Document Version:4.0,Most-Recent,Effective,CURRENT Page 4 of 209 Document Name RH205051 Synopsis Type Version Document Identifier Effective Date eldo_controlled 1.0; CURRENT; Most-Recent; Effective 090032d580d18c62 Reason For Issue To evaluate and compare the ability of a test toothpaste containing 0.6% zinc chloride (non-IPMP) to inhibit plaque glycolysis, and to inhibit plaque viability as assessed by area under the curve regrowth (AUCregrowth) and by AUClive:dead(0-90), compared to a non-SLS containing toothpaste and an SLS containing toothpaste. To make all other comparisons between products in AUCgly(0-90), AUCregrowth(0-90) and AUClive:dead(0-90). Design / Methodology: This was a single-centre, analyst and examiner (plaque sample collector)-blind, randomised, five-treatment, five-period cross -over study in healthy adult volunteers. At the screening visit, eligible subjects were provided with a standardised washout toothpaste to use at home, twice per day until the end of the study. Following screening, eligible subjects attended a plaque screening assessment visit where, having presented with overnight plaque (having not brushed their teeth since 11pm the evening before), a plaque sample was collected from the entire dentition using a swab. The acidgenicty of the plaque samples were determined and only subjects demonstrating plaque acidogenicity in the pH range 5.0-5.7 progressed to the treatment phase of the study. At each treatment visit having presented with overnight plaque (having not brushed their teeth since 11pm the evening before) subjects had an oral soft tissue (OST) examination. Subjects then had their dental plaque from their maxilliary left quadrant (from both facial and lingual surfaces) collected using a swab. Subjects swilled around their mouth with a pre-prepared slurry of toothpaste, ensuring the slurry contacted their entire dentition for 60 s before expectorating. Further dental plaque samples were swabbed at 15 minutes post-treatm ent (maxilliary right quadrant), 45 minutes post-treatment (mandibular left quadrant) and 90 minutes post-treatment (mandibular right quadrant). Subjects subsequent ly underwent a further OST examination and continued to attend further scheduled treatment visits until they had completed the study (allowing 2-10 between treatment visits). The ability for the plaque samples to generate acid (glycolysis) and to proliferate (regrowth) were assessed by standardising the plaque samples to an optical density of 0.2 cm-1, using tryptic soy broth (TSB) growth media supplemented with sucrose, and measuring the pH of the plaque suspension following 2 hours incubation at 37°C. The optical density was subsequently determined after a total of 4 hours of incubation at 37°C. The ratio of live to dead bacteria in the plaque samples were determined by Document Version:4.0,Most-Recent,Effective,CURRENT Page 5 of 209 Document Name RH205051 Synopsis Type Version Document Identifier Effective Date eldo_controlled 1.0; CURRENT; Most-Recent; Effective 090032d580d18c62 Reason For Issue addition of an aliquot of propidium iodide and Syto-9 dyes to the standardised plaque dispersion and the fluorescence of the result ing stained bacteria determined. Number of subjects (planned and analysed): It was planned that 45 subjects