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

Phase 2

Completed

• Conditions: Dental Caries
• Interventions: Drug: C16G2

• Registration Number: NCT02254993
• Lead Sponsor: Armata Pharmaceuticals, Inc.

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.

Detailed Description

Open-label, multiple arm, safety, microbiology and pharmacokinetic (PK) study in healthy adult male and female subjects 18-75 years of age conducted in two parts.

Part A of the study will evaluate up to 6 study arms, depending on the microbiology response evaluated. Before dosing of C16G2, eligible subjects will undergo professional dental prophylaxis on Day 0. Clinic visits for all Study Arms include Visit 1 (Screening/Days -21 to 0), Treatment Visits 2 through 6 (Baseline/Day 0 through Day 4), and follow-up Visits 7 through 11 (Day 5, 8, 12, 19 ± 1 and 33 ± 2).

All subjects will be assessed for safety and microbiology parameters for approximately 5 weeks. A subset of subjects in Study Arms 2 and 4 will be assessed for pharmacokinetic parameters. Part A of the study is no longer enrolling study subjects.

Part B of the study will evaluate up to 5 study arms, depending on the microbiology response evaluated during 2 interim microbiology reviews. Clinic visits for all study arms except Study Arm 5 include Visit 1 (Screening/Days -21 to 0), Visit 2 (Baseline/Day 0), Visits 3 through 17 (Days 1 through 6, morning and evening visits, and Days 7, 10 and 14). All subjects will be assessed for safety and microbiology parameters for approximately 2 weeks. Before dosing of C16G2, eligible subjects will undergo professional dental prophylaxis on Day 0. Study drug will be administered for 7 consecutive days. The Sponsor will perform a microbiology review to evaluate the S. mutans response in Study Arms 1 \& 2 and, if applicable, in Study Arms 3a or 3b. In Study Arm 5, subjects will receive multiple C16G2 doses on a single day and will be evaluated for safety, microbiology and pharmacokinetic parameters. Clinic visits for Study Arm 5 will include Visit 1 (Screening/Days -21 to 0), Visit 2 (Baseline/Day 0), Visit 3/Day 1 and Visit 4/Day 6.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-09-24
• Study First Submitted QC: 2014-09-30
• Study Start: 2014-10
• Study First Posted: 2014-10-02
• Primary Completion: 2015-06
• Study Completion: 2015-07
• Disposition First Submitted: 2016-12-15
• Disposition First Submitted QC: 2016-12-16
• Disposition First Posted: 2016-12-19
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-25
• Last Update Posted: 2019-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1- Part A	C16G2	One 30-minute C16G2 tray gel application (3.2 mg/mL) over the course of five days
Arm 5- Part A	C16G2	One 30-minute C16G2 tray gel application (1.6 mg/mL) over the course of five days
Arm 4- Part A	C16G2	One 4-hour C16G2 tray gel application (1.6 mg/mL) over the course of five days
Arm 5 - Part B	C16G2	Arm 5: Three manual brush gel applications followed by one tray gel application on Day 0, 3.2 mg/mL C16G2 gel concentration.
Arm 1 - Part B	C16G2	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.
Arm 2 - Part A	C16G2	One 4-hour C16G2 tray gel application (3.2 mg/mL) over the course of five days
Arm 3- Part A	C16G2	A single 4-hour C16G2 tray gel application (3.2 mg/mL)
Arm 6- Part A	C16G2	One 5-minute C16G2 tray gel application (3.2 mg/mL) over the course of five days
Arm 4a or 4b - Part B	C16G2	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
Arm 2 - Part B	C16G2	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.
Arm 3a or 3b or 3c - Part B	C16G2	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

Primary Outcome Measures

Name	Time	Method
To evaluate the safety of single and multiple C16G2 Gel administrations in healthy adult subjects	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	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

Secondary Outcome Measures

Name	Time	Method
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	Five study subjects each in Study Arms 2 and 4 (Part A) and six subjects in Study Arm 5 (Part B). Subjects will be assessed on a single day (Visit 6/Day 4 in Part A and Visit 2/Day 0 in Part B).
To assess total bacteria in saliva and dental plaque post-study drug administration	Visit 2 through Visit 11 (Part A only)	All subjects will be assessed for total bacteria levels for approximately 5 weeks (Part A only)
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	Five study subjects each in Study Arms 2 and 4 (Part A) and six subjects in Study Arm 5 (Part B). Subjects will be assessed on a single day (Visit 6/Day 4 in Part A and Visit 2/Day 0 in Part B).
Clearance (Cl) 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	Five study subjects each in Study Arms 2 and 4 (Part A) and six subjects in Study Arm 5 (Part B). Subjects will be assessed on a single day (Visit 6/Day 4 in Part A and Visit 2/Day 0 in Part B).
Elimination half life (t 1/2) 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	Five study subjects each in Study Arms 2 and 4 (Part A) and six subjects in Study Arm 5 (Part B). Subjects will be assessed on a single day (Visit 6/Day 4 in Part A and Visit 2/Day 0 in Part B).
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)	All subjects will be assessed for S. mutans levels for approximately 5 weeks (Part A) or 2 weeks (Part B)
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	Five study subjects each in Study Arms 2 and 4 (Part A) and six subjects in Study Arm 5 (Part B). Subjects will be assessed on a single day (Visit 6/Day 4 in Part A and Visit 2/Day 0 in Part B).
Volume of distribution (Vd) 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	Five study subjects each in Study Arms 2 and 4 (Part A) and six subjects in Study Arm 5 (Part B). Subjects will be assessed on a single day (Visit 6/Day 4 in Part A and Visit 2/Day 0 in Part B).

Trial Locations

Locations (2)

Jean Brown Research; 🇺🇸 Salt Lake City, Utah, United States

Plaza West II Dental Group; 🇺🇸 Kalispell, Montana, United States