A Phase 2 Study to Evaluate the Microbiology, Safety and Tolerability of C16G2 Varnish and Strip in Adolescent and Adult Subjects
Condition: Dental Caries
MeSH terms: Dental Caries
Intervention: C16G2; Placebo
Intervention description: C16G2; Varnish Placebo
Intervention MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Study Arms 1 and 2 will be enrolled in parallel followed by Study Arm 3.
Masking: Single (Participant)
Masking description: In the single-blind Study Arm 2, active and placebo will be identical in appearance and labeled in a blinded fashion
Enrollment: 20.0
Sex: All
Minimum age: 12 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      An open-label and single-blind phase 2 study to evaluate the oral microbiology, safety and
      tolerability of multiple C16G2 Varnish and Strip applications in male and female dental
      subjects 12-75 years of age. The study will compare multiple study drug administrations of
      C16G2 Varnish and/or C16G2 Strip in three study arms.

      In Study Arm 1 eight subjects will be enrolled in an open-label manner and will receive a
      daily dose of C16G2 Varnish application over 3 days followed by 14 doses of C16G2 Strip
      administered over 7 days. Following the three C16G2 Varnish applications, each subject will
      receive 7 days of AM and PM dosing with C16G2 Strip and will be followed for microbiology for
      up to 2 months after the last study drug administration.

      Study Arm 2 will enroll 12 subjects in a single-blind manner. Subjects will receive four
      C16G2 Varnish or Placebo applications over 7 days, followed by 3 additional weekly varnish
      administrations. Subjects will be followed for microbiology for up to 2 months after the last
      study drug administration.The treatment allocation will be 1:1 (6 subjects receiving C16G2
      Varnish, 6 subjects receiving Placebo).

      Study Arm 3 will be initiated based on the Sponsor's review of all microbiology data up to
      two week post last study drug administration from Study Arm 2. If initiated, Study Arm 3 will
      enroll 6 subjects in an open-label manner. Subjects will receive daily single doses of C16G2
      Varnish over 10 days, for a total of 10 doses and will be followed for microbiology for up to
      2 months after the last study drug administration.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females, 12-75 years of age

          2. Adults subjects provide written informed consent and adolescent subjects give written
             or verbal assent, as appropriate, and parent(s) or legal guardian(s) give written
             informed consent

          3. Female subjects of childbearing potential 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, relationship with a same sex partner or partner
             who has had a vasectomy at least six (6) months prior to the screening visit

          4. Negative urine pregnancy test in all females of childbearing potential (past menarche)

          5. Male subjects of sexual activity age: 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

          6. Healthy, as determined by the Investigator (in consultation with the Medical Monitor,
             as needed), based on medical and dental history, concurrent illnesses, laboratory
             results, concomitant medications, oral cavity assessment, and targeted physical
             examination (general, extraoral, head and neck) during Screening.

             Note: Subjects on a stable dose of medication may be eligible for screening and will
             be assessed by the medical monitor on a case-by-case basis.

          7. Have a minimum of 12 bicuspids and molars with a minimum of 8 molars and bicuspids NOT
             having restorations, crowns or sealants

          8. Demonstrated ability to expectorate ≥2 mL of stimulated saliva in 5 minutes

          9. Have a salivary S. mutans of 1.0 x 10^5 CFUs/mL or greater at Screening using mitis
             salivarius-bacitracin (MSB) agar plating

         10. Willing to refrain from using non-study dentifrice and other non-study oral care
             products (oral care rinses, fluoride products, etc.) during the study

         11. Willing to postpone elective dental procedures (e.g., dental cleanings) between
             Screening and final post-treatment visit (End of Study or Early Termination)

         12. Willing and able to comply with oral hygiene and diet instructions

         13. Able to communicate with the Investigator/study center personnel, understand and
             comply with the study requirements, and willing to return for protocol-specified
             visits at the appointed times

        Exclusion Criteria:

          1. Advanced periodontal disease

          2. Active caries lesion(s) within 30 days prior to study drug administration (confirmed
             by comprehensive caries examination including standard radiographs). Subjects
             presenting with insipient, non-cavitated lesion(s) are not excluded.

             Note: If radiographs are deemed appropriate for the study and taken within 6 months
             prior to the Screening visit, these may be used for determining eligibility and are
             not required to be repeated at Screening

          3. Partially erupted teeth where the entire crown is not erupted or an operculum is
             present

          4. 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

          5. Pathologic lesions of the oral cavity (suspicious or confirmed)

          6. Full dentures or permanent orthodontic appliances, e.g., braces, buccal or lingual
             brackets. Note: Partial dentures, removable retainers and night guards are not
             excluded, provided that they are cleaned regularly throughout the duration of the
             study

          7. Use of systemic antibiotics, topical oral antibiotics, any immunosuppressant therapy,
             and steroids, beginning 30 days prior to Screening until the end of study
             participation

          8. Medical history indicating the woman is pregnant, breastfeeding/lactating or has a
             positive urine pregnancy test

          9. 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)

         10. Participation in a previous C16G2 clinical trial having received either C16G2 Strip,
             C16G2 Varnish or Placebo Varnish

         11. 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, or jeopardize the safety of the subject or the validity of the
             study results