Phase 2, Safety & Microbiology Study of C16G2 in Multiple Oral Gel &/or Mouth Rinse Doses to Healthy Adults

Study Overview
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Brief Summary
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The focus of the study is to evaluate the safety of multiple study drug administrations and the study drug selectively reducing or eliminating a specific bacteria in the mouth. It will compare a liquid and gel product applied in different modes.

Detailed Description
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The study will evaluate the safety of multiple study drug administrations as assessed by adverse event monitoring, oral cavity assessments, targeted physical exams and vital signs. The study will also assess the study drug's ability to selectively reduce or eliminate specific bacteria in the mouth by comparing a liquid and gel product applied in different modes, such as mouth rinse administration and gel application using a dental tray, electric toothbrush or manual toothbrush administered over 7 consecutive days. Subjects will be followed for approximately 8 days after the last study drug administration for safety and microbiology.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Microbiology of C16G2 Administered in Multiple Oral Gel and/or Mouth Rinse Doses to Healthy Adult Subjects

Conditions
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Dental Caries

Intervention / Treatment
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* Drug: C16G2 Rinse
* Drug: Placebo
* Drug: C16G2 Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are eligible to participate if they meet the following criteria: Males and females, 18-75 years of age, inclusive, at the time the Informed Consent Form is signed Female subjects of childbearing potential, defined as not surgically sterile or at least two (2) years postmenopausal, must agree to use one of the following forms of contraception from screening through the last study visit: hormonal (oral, implant, or injection) begun >30 days prior to screening; barrier (condom, diaphragm, or cervical cap with spermicide); intrauterine device (IUD). Acceptable contraceptive options may also include abstinence, monogamous relationship with same sex partner or partner who has had a vasectomy at least six (6) months prior to the screening visit. Male subjects only: willing to use contraception or abstain from sexual activity beginning with the first exposure to study drug and continuing until discharged from the study due to completion or Early Termination. Healthy, as determined by the Investigator (in consultation with the Medical Monitor, as needed), based on medical and dental history, laboratory results, concomitant medications, oral cavity assessment, and targeted physical examination (extraoral, head and neck) during Screening Have a minimum of six unrestored bicuspids and molars with less than 50% of molars and bicuspids having restorations, crowns, sealants or are missing Demonstrated ability to expectorate ≥2 mL of stimulated saliva in 5 minutes Demonstrated ability to swish 10 mL of water for 4 minutes Have a salivary and dental plaque S. mutans of 2.0 x 10^4 colony forming unit (CFU)s/mL or greater at Screening using mitis salivarius-bacitracin (MSB) agar plating Willing to refrain from using non-study dentifrice and other non-study oral care products during the study Willing to postpone elective dental procedures (e.g. dental cleanings) between Screening and final post-treatment visit (End of Study or Early Termination) Able to understand and sign the Informed Consent Form prior to initiation of study procedures Able to communicate with the Investigator/study site personnel, understand and comply with the study requirements, and willing to return for protocol-specified visits at the appointed times Exclusion Criteria: Subjects are excluded from participation if any of the following apply: Advanced periodontal disease Active caries lesion(s) within 30 days prior to study drug administration (confirmed by dental examination and standard radiographs). Medical condition (e.g., artificial heart valve, history of infective endocarditis, cardiac transplant with valvular dysfunction, congenital heart disease or total joint replacement) for which antibiotics are recommended prior to dental visits and/or procedures Pathologic lesions of the oral cavity (suspicious or confirmed) Full or partial dentures, or orthodontic appliances, e.g. night guards, permanent retainers Impaired salivary function (unable to provide 2 mL of stimulated saliva within 5 minutes) Use of systemic antibiotics, topical oral antibiotics, or use of other drugs, which in the opinion of the Investigator could influence the study outcome, within 30 days prior to Screening Medical history indicating the woman is pregnant, breastfeeding/lactating or she has a positive urine pregnancy test Participation in a clinical trial or receipt of a non-FDA approved therapy within 30 days prior to study drug administration (depending on the specifics, participation in an observational study is not necessarily excluded) Presence of any condition or concurrent illness, which in the opinion of the Investigator, would compromise normal immune function (e.g., diabetes, rheumatoid arthritis, lupus, liver disease, organ transplant, etc.), interfere with the use of study dentifrice and oral care products, or interfere with the ability to comply with study requirements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Mouth Rinse Administration<br>Day 0, three consecutive C16G2 or placebo rinse administrations followed by three single C16G2 or placebo rinse administrations. Days 1 to 6 two additional C16G2 or placebo rinse administrations. | Drug: C16G2 Rinse<br>* Active rinses are 1.6 mg/mL C16G2.<br>Drug: Placebo<br>* Placebo is the vehicle without C16G2<br>|
| Other: Dental Tray Gel Administration<br>Day 0, two C16G2 or placebo gel dental tray applications and four C16G2 or placebo rinse administrations. Days 1 to 6, two C16G2 or placebo dental tray applications and two C16G2 or placebo rinse administrations. | Drug: C16G2 Rinse<br>* Active rinses are 1.6 mg/mL C16G2.<br>Drug: Placebo<br>* Placebo is the vehicle without C16G2<br>Drug: C16G2 Gel<br>* Active C16G2 Gel is 3.2 mg/mL<br>|
| Other: Electric Toothbrush Gel Application<br>Day 0, four C16G2 or placebo gel administrations applied with an electric toothbrush and four C16G2 or placebo rinse administrations. Days 1 to 6, two C16G2 or placebo gel administrations applied with a electric toothbrush and two C16G2 or placebo rinse administrations. | Drug: C16G2 Rinse<br>* Active rinses are 1.6 mg/mL C16G2.<br>Drug: Placebo<br>* Placebo is the vehicle without C16G2<br>Drug: C16G2 Gel<br>* Active C16G2 Gel is 3.2 mg/mL<br>|
| Other: Manual Toothbrush Gel Application<br>Day 0, four C16G2 or Placebo gel administrations applied with a manual toothbrush and four C16G2 or Placebo rinse administrations. Days 1 to 6, two C16G2 or Placebo gel administrations applied with a electric toothbrush and two C16G2 or Placebo rinse administrations. | Drug: C16G2 Rinse<br>* Active rinses are 1.6 mg/mL C16G2.<br>Drug: Placebo<br>* Placebo is the vehicle without C16G2<br>Drug: C16G2 Gel<br>* Active C16G2 Gel is 3.2 mg/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of multiple C16G2 Gel and/or C16G2 Rinse administrations in healthy adult subjects. | Safety will be assessed by comparing the incidence and duration of adverse events, clinically significant changes in vital signs, oral cavity assessments and targeted physical exams (C16G2 subjects in the four study arms vs. placebo). | Screening, Baseline, Days 1-7, & Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the targeted antimicrobial activity of C16G2 gel and rinse applications as measured by a reduction of dental plaque and salivary Streptococcus mutans (S. mutans). | Saliva and dental plaque samples will be assessed at screening and Days 1, 7 and 14 for S. mutans (C16G2 subjects in the four study arms vs. placebo). | Screening, Baseline, Days 1, 7 & 14 | 
| To assess total bacteria in dental plaque and saliva post-study drug. administration | Total bacteria will be assessed at screening, baseline and Days 1, 7 and 14 (C16G2 subjects in the four study arms vs. placebo). | Screening, Baseline, Days 1, 7 & 14 |