Clinical trial NCT01877421: Safety and Tolerability of Antiplaque Chewing Gum in a Gingivitis Population
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Plaque
Gingivitis
Keywords: Reducing plaque
Reducing gingivitis
safety
proof of concept
antiplaque chewing gum
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
First posted: 2013-06-13
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Safety and Tolerability of KSL-W as Measured by Soft Tissue Erythema, Ulceration and Sloughing (AEs and SAEs)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Proof of Concept of KSL-W in Reducing Plaque in Phase 2a
timeFrame: days 14, 28, 34
measure: Proof of Concept of KSL-W in Reducing Gingivitis in Phase 2a
timeFrame: days 14, 28, 34
measure: Gingival Bleeding on Probing (BOP) - Percent of Bleeding Sites Upon Probing in Phase 2a
timeFrame: days 0, 14, 28, 34
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Dentistry, Oral Health Research Institute
state: Indiana
Study officials:
affiliation: Oral Health Research Institute, Indiana University School of Dentistry
name: Domenick T Zero, DDS, MS
role: PRINCIPAL_INVESTIGATOR
References: