Phase 2, Open-Label Study for Safety, Microbiology and PK of Single or Multiple Oral C16G2 Gel Doses

NCT02254993 | Completed Phase 2

• 1 other identifier: C3J14-201B-00
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

Brief Summary

Part A: Open-label, multiple arm, safety, microbiology and pharmacokinetic (PK) study in healthy adult male and female subjects 18-75 years of age. All subjects will be assessed for safety and microbiology parameters. A subset of subjects will be assessed for pharmacokinetic parameters. No longer enrolling study subjects in Part A. Part B: Open-label, multiple arm, safety and microbiology study in healthy adult male and female subjects 18-75 years of age. All subjects will be assessed for safety, pharmacokinetic, and microbiology parameters.

Conditions

Dental Caries

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of single and multiple C16G2 Gel 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 in the 6 study arms

  All subjects will be monitored for safety for approximately 5 weeks (Visit 2 through Visit 11) in Part A, and for 2 weeks (Visit 2 through 17) in Part B of the study

Secondary Outcomes (8)

• To assess antimicrobial activity of C16G2 Gel applications as measured by a reduction in S. mutans in saliva and dental plaque

  Visit 2 through Visit 11 (Part A) or Visit 17 (Part B)

• To assess total bacteria in saliva and dental plaque post-study drug administration

  Visit 2 through Visit 11 (Part A only)

• Peak plasma concentration (Cmax) after multiple daily C16G2 Gel administrations

  Subjects will be assessed on a single day. PK time points are pre-study drug, during dosing at 5, 30 min, 2 and 4 hrs in Part A and prior to the 1st and 3rd brush, 5 min post 3rd brush, and 15 min and 1.5 hrs after tray

• Time to peak plasma concentration (Tmax) after multiple daily C16G2 Gel administrations

  Subjects will be assessed on a single day. PK time points are pre-study drug, during dosing at 5, 30 min, 2 and 4 hrs in Part A and prior to the 1st and 3rd brush, 5 min post 3rd brush, and 15 min and 1.5 hrs after tray

• Area under the curve (AUC) after multiple daily C16G2 Gel administrations

  Subjects will be assessed on a single day. PK time points are pre-study drug, during dosing at 5, 30 min, 2 and 4 hrs in Part A and prior to the 1st and 3rd brush, 5 min post 3rd brush, and 15 min and 1.5 hrs after tray

Study Arms (11)

Arm 1- Part A

EXPERIMENTAL

One 30-minute C16G2 tray gel application (3.2 mg/mL) over the course of five days

Drug: C16G2

Arm 2 - Part A

EXPERIMENTAL

One 4-hour C16G2 tray gel application (3.2 mg/mL) over the course of five days

Drug: C16G2

Arm 3- Part A

EXPERIMENTAL

A single 4-hour C16G2 tray gel application (3.2 mg/mL)

Drug: C16G2

Arm 4- Part A

EXPERIMENTAL

One 4-hour C16G2 tray gel application (1.6 mg/mL) over the course of five days

Drug: C16G2

Arm 5- Part A

EXPERIMENTAL

One 30-minute C16G2 tray gel application (1.6 mg/mL) over the course of five days

Drug: C16G2

Arm 6- Part A

EXPERIMENTAL

One 5-minute C16G2 tray gel application (3.2 mg/mL) over the course of five days

Drug: C16G2

Arm 1 - Part B

EXPERIMENTAL

Four manual brush gel applications on Day 0 followed by twice daily manual brush gel applications (Days 1 through 6); total of 7-day study drug administration, 3.2 mg/mL C16G2 gel concentration.

Drug: C16G2

Arm 2 - Part B

EXPERIMENTAL

Three manual brush gel applications followed by one tray gel application on Day 0. One manual brush application in the morning and one tray gel application in the evening on Days 1 through 6; total of 7-day study drug administration, 3.2 mg/mL C16G2 gel concentration.

Drug: C16G2

Arm 3a or 3b or 3c - Part B

EXPERIMENTAL

Based on the microbiology review, one of 3 study arms will be conducted: Arm 3a: Four manual brush gel applications on Day 0 followed by twice daily manual brush applications (Days 1 through 6); total of 7-day study drug administration, lower C16G2 concentration of 1.6 mg/mL Arm 3b: Three manual brush gel applications followed by one tray gel application on Day 0. One manual brush application in the morning and one tray gel application in the evening on Days 1 through 6; total of 7-day study drug administration, lower C16G2 concentration of 1.6 mg/mL Arm 3c: Three daily manual brush and/or tray gel applications for 7 days, lower C16G2 concentration of 1.6 mg/mL

Drug: C16G2

Arm 4a or 4b - Part B

EXPERIMENTAL

Based on the microbiology review, one of 2 study arms will be conducted: Arm 4a: Four manual brush gel applications on Day 0 followed by twice daily manual brush applications (Days 1 through 6); total of 7-day study drug administration, C16G2 concentration of 1.6 mg/mL and lower gel volume Arm 4b: Three manual brush gel applications followed by one tray gel application on Day 0. One manual brush application in the morning and one tray gel application in the evening on Days 1 through 6; total of 7-day study drug administration, lower C16G2 concentration of 1.6 mg/mL and lower gel volume

Drug: C16G2

Arm 5 - Part B

EXPERIMENTAL

Arm 5: Three manual brush gel applications followed by one tray gel application on Day 0, 3.2 mg/mL C16G2 gel concentration.

Drug: C16G2

Interventions

C16G2 DRUG

antimicrobial peptide

Also known as: C16G2 (1.6 mg/mL), C16G2 (3.2 mg/mL)

Arm 1 - Part B; Arm 1- Part A; Arm 2 - Part A; Arm 2 - Part B; Arm 3- Part A; Arm 3a or 3b or 3c - Part B; Arm 4- Part A; Arm 4a or 4b - Part B; Arm 5 - Part B; Arm 5- Part A; Arm 6- Part A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, 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, concurrent illnesses, 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 ≤50% of molars and bicuspids having restorations, crowns, sealants or are missing
• Demonstrated ability to expectorate ≥2 mL of stimulated saliva in 5 minutes
• Have a salivary S. mutans of 2.0 x 10\^4 CFUs/mL or greater (Part A) or 1.0 x 10\^5 colony forming unit (CFU)/mL or greater (Part B) 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

You may not qualify if:

• 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
• 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)
• Prior participation in a C16G2 clinical trial and known to have received C16G2 active gel or mouth rinse (Note: placebo subjects are not 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

Sponsors & Collaborators

• Armata Pharmaceuticals, Inc.: lead

Study Sites (2)

Plaza West II Dental Group

Kalispell, Montana, 59901, United States

Location

Jean Brown Research

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Conditions

Dental Caries

Condition Hierarchy (Ancestors)

Tooth Demineralization; Tooth Diseases; Stomatognathic Diseases

Study Officials

• Adam D Marberger, DDS

  Study Center PI

  PRINCIPAL INVESTIGATOR

• John F Pittaway, DMD

  Study Center PI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2014
• First Posted: October 2, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 1, 2019

Record last verified: 2019-07

Locations

US (2)