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 (APCG)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by U.S. Army Medical Research and Materiel Command
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01877421
First received: May 14, 2013
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Plaque
Gingivitis
Drug: 2 mg KSL-W
Drug: 4 mg KSL-W
Drug: 6 mg KSL-W
Drug: 10 mg KSL-W
Drug: 20 mg KSL-W
Drug: 30 mg KSL-W
Drug: 50 mg KSL-W
Drug: 75 mg KSL-W
Drug: 100 mg KSL-W
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Safety and tolerability of KSL-W as measured by soft tissue erythema, ulceration and sloughing. [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Proof of concept of KSL-W in reducing plaque as measured by Turesky modification of the Quigley-Hein Plaque Index(PI). [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Proof of concept of KSL-W in reducing gingivitis as measured by modified gingival index (MGI) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Proof of concept of KSL-W in reducing plaque as measured percent of bleeding sites upon probing (BOP) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 137
Study Start Date: February 2014
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2 mg KSL-W
one 2 mg KSL-W tablet at day 0 at Phase 1
Drug: 2 mg KSL-W
Experimental: 4 mg KSL-W
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
Experimental: 6 mg KSL-W
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
Experimental: 10 mg KSL-W
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
Experimental: 20 mg KSL-W
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
Experimental: 30 mg KSL-W
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
Experimental: 50 mg KSL-W
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
Experimental: 75 mg KSL-W
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
Experimental: 100 mg KSL-W
one 100 mg KSL-W tablet at day 0 at Phase 1
Drug: 100 mg KSL-W
Placebo Comparator: Placebo
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01877421

Contacts
Contact: Domenick T Zero, DDS, MS 240-457-0668 dzero@iu.edu
Contact: Ana G Odont, DDS, MSD 317-274-8822 amgutier@iu.edu

Locations
United States, Indiana
Indiana University School of Dentistry, Oral Health Research Institute Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Domenick T Zero, DDS, MS    317-274-5429    dzero@iu.edu   
Contact: Ana G Odont, DDS, MSD    317-274-8822    amgutier@iu.edu   
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Domenick T Zero, DDS, MS Oral Health Research Institute, Indiana University School of Dentistry
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01877421     History of Changes
Other Study ID Numbers: S-11-14
Study First Received: May 14, 2013
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
Reducing plaque
Reducing gingivitis
safety
proof of concept
antiplaque chewing gum

Additional relevant MeSH terms:
Gingivitis
Gingival Diseases
Periodontal Diseases
Mouth Diseases
Stomatognathic Diseases

ClinicalTrials.gov processed this record on September 18, 2014