Safety and Tolerability of Antiplaque Chewing Gum in a Gingivitis Population (APCG)

February 11, 2020 updated by: U.S. Army Medical Research and Development Command

A Double-Blind, Randomized, Controlled, Dose Escalation Clinical Trial of an Antiplaque Chewing Gum - Phase 1 Safety and Tolerability and Phase 2a Safety, Tolerability, and Proof of Concept in a Gingivitis Population

This study is to assess the safety and tolerability of single doses and multiple doses in reducing plaque and gingivitis when delivered in a chewing gum formulation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a Phase 1/2a placebo-controlled, double-blind, randomized, dose-escalation study to evaluate the safety and proof of concept of Antiplaque Chewing Gum. This is a 2-part trial with 9 dosing cohorts in Phase 1 and 7 dosing cohorts in Phase 2a. For both phases, the oral soft (OST) and oral hard tissues (OHT) will be examined. Changes from baseline, such as soft tissue erythema, ulceration and sloughing, will be noted and assessments will be made by the principal investigator as to whether they might be attributable to the antiplaque chewing gum.

In the Phase 2a portion of the study, the efficacy of the antiplaque chewing gum in reducing existing supragingival plaque and gingivitis will also be assessed. Plaque will be assessed using the Turesky Modification of the Quigley-Hein Plaque Index (PI, Turesky et al-1970) and gingivitis will be assessed using both the Modified Gingival Index (MGI, Lobene et al-1986) and the percent of bleeding sites on gentle probing (BOP) using the methods described in Ainamo and Bay-1975.

Study Type

Interventional

Enrollment (Actual)

135

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Dentistry, Oral Health Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Subjects must meet all of the following criteria to be included in the Phase 1 portion of the study:

  • Males and females between 18 and 64 years of age
  • A negative urine pregnancy test and willingness to use a reliable form of contraception for the duration of the study (females of childbearing potential only), with reliable contraception defined as:

Abstinence Oral contraceptive, either estrogen progesterone combined, or progesterone alone Injectable progesterone Implants of levonorgestrel Estrogenic vaginal ring Percutaneous contraceptive patches Intrauterine device or intrauterine system Double barrier method [condom or occlusive cap (diaphragm or cervical vault caps) plus spermicidal agent (foam, gel, film, cream, suppository)] Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject

  • Good health, as determined by pertinent medical history, physical examination, vital signs, and clinical safety laboratory evaluations
  • A minimum of 16 natural teeth with 2 scorable surfaces (facial and lingual) per tooth Sufficient number of opposing posterior teeth to chew on both sides of the mouth as determined by the examining dentist Teeth that have gross caries, full crowns or extensive restorations on facial and/or lingual surfaces, orthodontic bands, and third molars are not included in the tooth count
  • Ability to comprehend and a willingness to sign an informed consent, which includes the Authorization for the Release of Health Information document
  • Willingness to comply with all study procedures

Phase 2a Inclusion Criteria

Subjects must meet all the criteria for the phase 1 portion of the study, and in addition must:

  • Have mild to moderate gingivitis and plaque MGI of 1.8 or greater (Ainamo and Bay-1975) PI of 1.95 or greater (Turesky et al-1970)
  • Willing to forgo any optional dental procedures during the study period, such as dental prophylaxis or teeth whitening

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

  • Acute or chronic medical conditions, organ system disease, or medications that, in the principal investigator's opinion, would impair the subject's ability to participate
  • TMD
  • Self-reported use of tobacco products
  • Use of anticoagulant medications (eg clopidogrel)
  • Gross oral pathology, including widespread caries or chronic neglect, extensive restoration, pre-existing gross plaque or calculus, or soft or hard tissue tumor of the oral cavity
  • Orthodontic appliances or removable partial dentures that will compromise the ability of the potential subject to participate in the study
  • Periodontitis as indicated periodontal pockets greater than 4 millimeters on more than one site
  • Receipt of any investigational drug/test product within 30 days prior to study entry
  • Receipt of antibiotics within 30 days prior to study entry
  • Need for antibiotic prophylaxis prior to invasive dental procedures
  • Receipt of daily anti-inflammatory therapy [eg nonsteroidal anti-inflammatory drugs (NSAID), tumor necrosis factor (TNF) alpha blockers] within 30 days prior to study entry
  • Receipt of prescription antibacterial oral products (eg products containing chlorhexidine) within 30 days prior to study entry
  • Pregnant or breast-feeding female
  • Clinically significant abnormal laboratory tests as determined by the principal investigator
  • An employee of the study site directly involved with the study
  • Inability to comply with assigned treatment regimen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
Cetylpyridinium chloride (CPC) as an additive, isomalt as a bulk sweetener, peppermint powder for flavoring, sucralose as an intense sweetener, colloidal silicon dioxide is a flow enhancer, magnesium stearate as a process aid, and the proprietary gum base formulation.
Experimental: 2 mg KSL-W (Phase 1, 1a)
one 2 mg KSL-W tablet at day 0 at Phase 1
Drug: 2 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 4 mg KSL-W (Phase 1, 2a; Phase 2a, 1b)
one 4 mg KSL-W tablet on day 0 at both Phase 1 and Phase 2a. one 4 mg KSL-W tablet on days 1-6; two 4 mg KSL-W tablets on days 7-13 and days 14-20; and three 4 mg tablets at days 21-27 at Phase 2a.
Drug: 4 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 6 mg KSL-W (Phase 1, 3a; Phase 2a, 2b)
One 6 mg KSL-W tablet on day 0 at both Phase 1 and Phase 2a. One 6 mg KSL-W tablet on days 1-6; two 6 mg KSL-W tablets on days 7-13 and days 14-20; and three 6 mg tablets at days 21-27 at Phase 2a.
Drug: 6 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 10 mg KSL-W (Phase 1, 4a; Phase 2a, 3b)
One 10 mg KSL-W tablet on day 0 at both Phase 1 and Phase 2a. One 10 mg KSL-W tablet on days 1-6; two 10 mg KSL-W tablets on days 7-13 and days 14-20; and three 10 mg tablets at days 21-27 at Phase 2a.
Drug: 10 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 20 mg KSL-W (Phase 1, 5a; Phase 2a, 4b)
One 20 mg KSL-W tablet on day 0 at both Phase 1 and Phase 2a. One 20 mg KSL-W tablet on days 1-6; two 20 mg KSL-W tablets on days 7-13 and days 14-20; and three 20 mg tablets at days 21-27 at Phase 2a.
Drug: 20 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 30 mg KSL-W (Phase 1, 6a; Phase 2a, 5b)
One 30 mg KSL-W tablet on day 0 at both Phase 1 and Phase 2a. One 30 mg KSL-W tablet on days 1-6; two 30 mg KSL-W tablets on days 7-13 and days 14-20; and three 30 mg tablets at days 21-27 at Phase 2a.
Drug: 30 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 50 mg KSL-W (Phase 1, 7a; Phase 2a, 6b)
One 50 mg KSL-W tablet on day 0 at both Phase 1 and Phase 2a. One 50 mg KSL-W tablet on days 1-6; two 50 mg KSL-W tablets on days 7-13 and days 14-20; and three 50 mg tablets at days 21-27 at Phase 2a.
Drug: 50 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 75 mg KSL-W (Phase 1, 8a; Phase 2a, 7b)
One 75 mg KSL-W tablet on day 0 at both Phase 1 and Phase 2a. One 75 mg KSL-W tablet on days 1-6; two 75 mg KSL-W tablets on days 7-13 and days 14-20; and three 75 mg tablets at days 21-27 at Phase 2a.
Drug: 75 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum
Experimental: 100 mg KSL-W (Phase 1, 9a)
one 100 mg KSL-W tablet at day 0 at Phase 1
Drug: 100 mg KSL-W
Other Names:
  • Antiplaque Chewing Gum

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of KSL-W as Measured by Soft Tissue Erythema, Ulceration and Sloughing (AEs and SAEs)
Time Frame: Up to 28 days
Occurrence of local oral mucosal reactions, systemic reactions such as fever, nausea, headache, and changes in blood pressure, clinical laboratory measures of safety, and serious total body reactions will be assessed (AEs and SAEs)
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proof of Concept of KSL-W in Reducing Plaque in Phase 2a
Time Frame: days 14, 28, 34

Data summarizes plaque index scores changes from baseline. Supragingival plaque will be assessed after the MGI and BOP assessments and following use of a disclosing solution on the facial (buccal) and lingual surfaces of a minimum of 16 scorable teeth according to the criteria of the Turesky modification of the Quigley-Hein Plaque Index.

Quigley-Hein Plaque Index Scores with Turesky Modifications:

0 No plaque

  1. Separate flecks of plaque at the cervical margin of the tooth
  2. A thin continuous band of plaque (up to one mm) at the cervical margin of the tooth
  3. A band of plaque wider than one mm but covering less than one-third of the crown of the tooth
  4. Plaque covering at least one-third but less than two thirds of the crown of the tooth
  5. Plaque covering two-thirds or more of the crown of the tooth
days 14, 28, 34
Proof of Concept of KSL-W in Reducing Gingivitis in Phase 2a
Time Frame: days 14, 28, 34

Data summarizes gingival index scores changes from baseline in phase 2a. Gingivitis will be assessed using both the MGI (Modified Gingival Index) and the Gingival Bleeding Index (BOP) The Modified Gingival Index assesses the buccal and lingual gingivae and interdental papillae.

Modified Gingival Index Scores:

0 Absence of inflammation

  1. Mild inflammation; slight change in color, little change in texture of any portion of but not the entire marginal or papillary gingival unit
  2. Mild inflammation; criteria as above but involving the entire marginal or papillary gingival unit
  3. Moderate inflammation; glazing, redness, edema and/or hypertrophy of the marginal or papillary gingival unit
  4. Severe inflammation; marked redness, edema and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration.
days 14, 28, 34
Gingival Bleeding on Probing (BOP) - Percent of Bleeding Sites Upon Probing in Phase 2a
Time Frame: days 0, 14, 28, 34

Proof of concept of KSL-W in reducing plaque as measured by percent of bleeding sites upon probing (BOP) in phase 2a.

Gingivitis will be assessed using both the MGI (Modified Gingival Index) and the Gingival Bleeding Index (BOP). The Modified Gingival Index assesses the buccal and lingual gingivae and interdental papillae. The Gingival Bleeding Index assesses the percentage of sites that bleed on gentle probing. A periodontal probe (HU-Friedy UNC 15) will be gently inserted into the gingival sulcus until resistance is felt at mid-facial (buccal), mid-lingual, mesial, and distal interproximal sites of all scorable teeth, with the exception of the most posterior distal sites. Presence or absence of bleeding will be recorded for each site and the percentage of bleeding sites per subject will serve as the unit of analysis.
days 0, 14, 28, 34

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

U.S. Army Medical Research and Development Command

Investigators

  • Principal Investigator: Domenick T Zero, DDS, MS, Oral Health Research Institute, Indiana University School of Dentistry

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2014

Primary Completion (Actual)

August 25, 2015

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

May 14, 2013

First Submitted That Met QC Criteria

June 10, 2013

First Posted (Estimate)

June 13, 2013

Study Record Updates

Last Update Posted (Actual)

February 13, 2020

Last Update Submitted That Met QC Criteria

February 11, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S-11-14

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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