Safety, Efficacy and Treatment Regimen Study of ST266 in Subjects With Moderate to Severe Periodontitis

• Sponsor: Noveome Biotherapeutics, formerly Stemnion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02761993
• Collaborator: (none)
• Enrollment: 151
• Locations: 6
• Arms: 3
• Actual Duration (Months): 18
• Patients Per Site: 25.2
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether ST266 will reduce pocket depth (PD) as an adjunctive to scaling and root planing (SRP) in subjects with moderate to severe periodontal disease.

Condition or Disease	Intervention/Treatment	Phase
Periodontal Disease	Biological: ST266; Drug: Saline (0.9% NaCl)	Phase 2

Detailed Description

The study is a 9-month, randomized, double-blind, parallel-design study of subjects with existing moderate to severe periodontal disease randomly assigned to one of three groups. The primary endpoint of PD change will be evaluated following 9 months of treatment. Subjects will be followed for 9 months for safety and radiographic evaluations.

Subjects who meet inclusion criteria will be randomized to one of three treatment groups.

Randomization will be stratified by site and smoker status (never smoked or quit smoking more than two years ago vs. has smoked within the last two years). Randomization will be blocked such that assignment to treatment groups both within sites and within smoker status will be approximately even (1:1:1). Treatment will be initiated after SRP.

All subjects will be evaluated at baseline and Days 1, 15, 30, 60, 90, 180, and 270.

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Efficacy, and Treatment Regimen of ST266 in Subjects With Moderate to Severe Periodontitis
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group 1 Group 1 received ST266 treatment daily on Days 1 through 5, 8 through 12, 22, and 30, and then monthly for 7 months (Days 60, 90, 120, 150, 180, 210, and 240).	Biological: ST266; 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
Active Comparator: Group 2 Group 2 received ST266 treatment 2x/week (with at least 1 day between treatments) for the first 3 months, and then monthly for 5 months (Days 120, 150, 180, 210, and 240).	Biological: ST266; 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
Placebo Comparator: Group 3 Group 3 received commercially available sterile saline (0.9% sodium chloride) according to the same schedule as Group 1.	Drug: Saline (0.9% NaCl); Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).

Outcome Measures

Primary Outcome Measures

1. Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline [Baseline; 9 months]

   The primary efficacy endpoint of this study is the change from baseline in the PD at 9 months (Day 270) for those pockets ≥6 mm at baseline.

Secondary Outcome Measures

1. Changes in Clinical Attachment Level (CAL) [Baseline, 9 months]

   Change in Clinical Attachment Level (CAL) (the measurement of the position of the soft tissue in relation to the cemento-enamel junction (CEJ) that is a fixed point, using probing depth and the distance from the gingival margin to the CEJ.) from baseline in CAL at 9 months (Day 270) in tooth sites with baseline PD ≥ 6mm.

2. Bleeding on Probing (BOP) [Baseline and 9 months]

   A secondary efficacy endpoint of this study is change from baseline in BOP at 9 months (Day 270) with BOP for each subject calculated as the percentage of tooth sites in the whole mouth with BOP.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of signed, written informed consent prior to participation in any study-related procedures.

• Good general health as evidenced by medical history.

• Between 18 and 85 years of age at time of informed consent signature.

• Male or female.

• Minimum of 18 teeth, excluding third molars.

• Having moderate to severe periodontal disease according to AAP definition (at least 6 teeth ≥6 mm PD and ≥3 mm CAL at baseline).

• Having >30 percent bleeding sites upon probing.

• Willing to abstain from chewing gums and other mouth rinses for the study duration.

• Ability and willingness to attend all study visits and comply with all study visits and comply with all study procedures and requirements.

• Willingness to abstain from routine dental care.

• For women with reproductive potential, willingness to use highly effective contraception (e.g. licensed hormonal contraception, intrauterine device, abstinence, or vasectomy in partner).

Exclusion Criteria:

• Presence of orthodontic appliances.

• A soft or hard tissue tumor of the oral cavity.

• Any dental condition that requires immediate treatment, such as carious lesions.

• Participation in any other clinical study within 30 days of screening or during the study.

• Pregnancy or lactation. If a subject meets this criterion, she may be rescreened for study participation when she no longer meets this criterion.

• Antibiotic therapy within the last 30 days.

• Chronic use (≥3 times/week) of anti-inflammatory medications (e.g., non-steroidal anti inflammatory drugs, steroids). Low-dose aspirin (less than 325 mg daily) is allowed.

• Immunocompromised subjects.

• Subjects with cancer or a history of cancer within the last 5 years of screening.

• Any medical history or any concomitant medication that might affect the assessment of the study treatment or periodontal tissues, such as diabetes, nifedipine, phenytoin (Dilantin), or anticoagulant medications (e.g., warfarin [Coumadin] etc.).

• Involvement in the planning or conduct of the study.

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or interfere with interpretation of the subject's study results.

• Previous randomization for treatment in the present study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham School of Dentistry	Birmingham	Alabama	United States	35294
2	Oral Health Research Institute	Indianapolis	Indiana	United States	46202
3	Forsyth Institute	Cambridge	Massachusetts	United States	02142
4	Columbia University College of Dental Medicine	New York	New York	United States	10032
5	Stony Brook School of Dental Medicine	Stony Brook	New York	United States	11794-8703
6	University of North Carolina at Chapel Hill School of Dentistry	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• Noveome Biotherapeutics, formerly Stemnion

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 8, 2017
• Statistical Analysis Plan - Oct 2, 2017

More Information

Publications

None provided.

• Responsible Party: Noveome Biotherapeutics, formerly Stemnion
• ClinicalTrials.gov Identifier: NCT02761993
• Other Study ID Numbers: ST266-PERIO-201
• First Posted: May 4, 2016
• Last Update Posted: Jul 22, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Periodontitis; Periodontal Diseases

Study Results

Participant Flow

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Group 1 received ST266 treatment daily on Days 1 through 5, 8 through 12, 22, and 30, and then monthly for 7 months (Days 60, 90, 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 2 received ST266 treatment 2x/week (with at least 1 day between treatments) for the first 3 months, and then monthly for 5 months (Days 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 3 received commercially available sterile saline (0.9% sodium chloride) according to the same schedule as Group 1. Saline (0.9% NaCl): Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
Period Title: Overall Study
STARTED	52	49	50
COMPLETED	50	43	46
NOT COMPLETED	2	6	4

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Group 3	Total
Arm/Group Description	Group 1 received ST266 treatment daily on Days 1 through 5, 8 through 12, 22, and 30, and then monthly for 7 months (Days 60, 90, 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 2 received ST266 treatment 2x/week (with at least 1 day between treatments) for the first 3 months, and then monthly for 5 months (Days 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 3 received commercially available sterile saline (0.9% sodium chloride) according to the same schedule as Group 1. Saline (0.9% NaCl): Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Total of all reporting groups
Overall Participants	52	49	50	151
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.4 (12.52)	51.6 (11.91)	52.5 (11.16)	51.1 (11.88)
Age, Customized (Count of Participants)
≤ 55 years	34 65.4%	29 59.2%	28 56%	91 60.3%
55 - ≤ 65 years	13 25%	12 24.5%	16 32%	41 27.2%
> 65 years	5 9.6%	8 16.3%	6 12%	19 12.6%
Sex: Female, Male (Count of Participants)
Female	22 42.3%	21 42.9%	25 50%	68 45%
Male	30 57.7%	28 57.1%	25 50%	83 55%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 25%	13 26.5%	9 18%	35 23.2%
Not Hispanic or Latino	39 75%	36 73.5%	40 80%	115 76.2%
Unknown or Not Reported	0 0%	0 0%	1 2%	1 0.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	4 7.7%	0 0%	5 10%	9 6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	9 17.3%	14 28.6%	15 30%	38 25.2%
White	25 48.1%	23 46.9%	22 44%	70 46.4%
More than one race	1 1.9%	2 4.1%	1 2%	4 2.6%
Unknown or Not Reported	13 25%	10 20.4%	7 14%	30 19.9%
Smoking Status (Count of Participants)
Smoker	13 25%	14 28.6%	13 26%	40 26.5%
Non-Smoker	39 75%	35 71.4%	37 74%	111 73.5%

Outcome Measures

1. Primary Outcome

Title	Changes in Pocket Depth (PD) for Those Pockets ≥ 6 mm at Baseline
Description	The primary efficacy endpoint of this study is the change from baseline in the PD at 9 months (Day 270) for those pockets ≥6 mm at baseline.
Time Frame	Baseline; 9 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) population: All randomized subjects with non-missing data for a given endpoint and time point. If the proportion of subjects (and oral sites) with missing data is ≤5 percent, as we expect it to be, for these analyses we will use the non-missing data and ignore the missingness.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Group 1 received ST266 treatment daily on Days 1 through 5, 8 through 12, 22, and 30, and then monthly for 7 months (Days 60, 90, 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 2 received ST266 treatment 2x/week (with at least 1 day between treatments) for the first 3 months, and then monthly for 5 months (Days 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 3 received commercially available sterile saline (0.9% sodium chloride) according to the same schedule as Group 1. Saline (0.9% NaCl): Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
Measure Participants	52	49	50
Measure Tooth-Sites	1323	1338	1374
Pocket Depth (mm) - Baseline	6.6 (0.93)	6.6 (1.02)	6.7 (1.03)
Pocket Depth (mm) - Day 270	4.5 (1.45)	4.6 (1.53)	4.5 (1.49)
Pocket Depth (mm) - Change from Baseline	-2.1 (1.40)	-2.0 (1.39)	-2.1 (1.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.341
	Comments	Since there were two (2) primary hypotheses, Bonferroni corrections were used to control for multiplicity, with p < 0.025 considered significant.
	Method	Generalized Estimating Equation
	Comments	Generalized estimating equations (GEE) method with a linear link and exchangeable covariance matrix (with subject correlation structure)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.774
	Comments	Since there were two (2) primary hypotheses, Bonferroni corrections were used to control for multiplicity, with p < 0.025 considered significant.
	Method	Generalized Estimating Equations
	Comments	Generalized estimating equations (GEE) method with a linear link and exchangeable covariance matrix (with subject correlation structure)

2. Secondary Outcome

Title	Changes in Clinical Attachment Level (CAL)
Description	Change in Clinical Attachment Level (CAL) (the measurement of the position of the soft tissue in relation to the cemento-enamel junction (CEJ) that is a fixed point, using probing depth and the distance from the gingival margin to the CEJ.) from baseline in CAL at 9 months (Day 270) in tooth sites with baseline PD ≥ 6mm.
Time Frame	Baseline, 9 months

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) population: All randomized subjects with non-missing data for a given endpoint and time point. If the proportion of subjects (and oral sites) with missing data is ≤5 percent, as we expect it to be, for these analyses we will use the non-missing data and ignore the missingness.

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Group 1 received ST266 treatment daily on Days 1 through 5, 8 through 12, 22, and 30, and then monthly for 7 months (Days 60, 90, 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 2 received ST266 treatment 2x/week (with at least 1 day between treatments) for the first 3 months, and then monthly for 5 months (Days 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 3 received commercially available sterile saline (0.9% sodium chloride) according to the same schedule as Group 1. Saline (0.9% NaCl): Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
Measure Participants	52	49	50
Measure Tooth-Sites	1323	1338	1374
Clinical Attachment Level (mm) - Baseline	6.7 (1.69)	6.8 (1.62)	6.7 (1.7)
Clinical Attachment Level (mm) - Day 270	5.1 (2.01)	5.1 (1.92)	5.1 (2.05)
Clinical Attachment Level (mm) - Difference from Baseline	-1.6 (1.48)	-1.7 (1.79)	-1.6 (1.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.501
	Comments	Since there were two (2) primary hypotheses, Bonferroni corrections were used to control for multiplicity, with p < 0.025 considered significant.
	Method	Generalized Estimating Equations
	Comments	Generalized estimating equations (GEE) method with a linear link and exchangeable covariance matrix (with subject correlation structure)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.486
	Comments	Since there were two (2) primary hypotheses, Bonferroni corrections were used to control for multiplicity, with p < 0.025 considered significant.
	Method	Generalized Estimating Equations
	Comments	Generalized estimating equations (GEE) method with a linear link and exchangeable covariance matrix (with subject correlation structure)

3. Secondary Outcome

Title	Bleeding on Probing (BOP)
Description	A secondary efficacy endpoint of this study is change from baseline in BOP at 9 months (Day 270) with BOP for each subject calculated as the percentage of tooth sites in the whole mouth with BOP.
Time Frame	Baseline and 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Group 1 received ST266 treatment daily on Days 1 through 5, 8 through 12, 22, and 30, and then monthly for 7 months (Days 60, 90, 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 2 received ST266 treatment 2x/week (with at least 1 day between treatments) for the first 3 months, and then monthly for 5 months (Days 120, 150, 180, 210, and 240). ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).	Group 3 received commercially available sterile saline (0.9% sodium chloride) according to the same schedule as Group 1. Saline (0.9% NaCl): Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
Measure Participants	52	49	50
Bleeding on Probing (%) - Baseline	67 (17.51)	62.8 (15.84)	67.5 (19.15)
Bleeding on Probing (%) - Day 270	40.9 (20.80)	38.8 (19.96)	41.7 (25.2)
Bleeding on Probing (%) - Change from Baseline	-26.2 (18.52)	-24.0 (21.23)	-25.8 (19.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.816
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 2, Group 3
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.706
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Events that occurred after first treatment dose date and prior to the last treatment dose date + 30 days, a total of up to 9 months
Arm/Group Title	Group 1		Group 2		Group 3
Arm/Group Description	Group 1: 1XST266 dosed as per regimen 1. ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).		Group 2: 1XST266 as per regimen 2. ST266: 1X ST266 applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. ST266 will be applied directly to the marginal gingiva around each tooth (buccal and lingual).		Group 3: Placebo dosed as per regimen 1. Saline (0.9% NaCl): Saline applied in a dose of 20 microliters per tooth. Total daily dose will be less than 1 milliliter. Saline will be applied directly to the marginal gingiva around each tooth (buccal and lingual).
All Cause Mortality
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/49 (0%)		0/50 (0%)
Serious Adverse Events
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/52 (3.8%)		2/49 (4.1%)		2/50 (4%)
Hepatobiliary disorders
Cholecystitis	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Immune system disorders
Anaphylactic shock	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Infections and infestations
Arthritis bacterial	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Endometrial cancer	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Pancreatic carcinoma	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Group 1		Group 2		Group 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/52 (55.8%)		27/49 (55.1%)		24/50 (48%)
Eye disorders
Eye swelling	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Ocular hyperaemia	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Gastrointestinal disorders
Gingival pain	3/52 (5.8%)	3	1/49 (2%)	1	2/50 (4%)	2
Sensitivity of teeth	1/52 (1.9%)	1	2/49 (4.1%)	2	3/50 (6%)	3
Toothache	3/52 (5.8%)	3	1/49 (2%)	1	2/50 (4%)	2
Aphthous ulcer	2/52 (3.8%)	2	2/49 (4.1%)	2	0/50 (0%)	0
Gingival erythema	1/52 (1.9%)	1	0/49 (0%)	0	2/50 (4%)	2
Leukoplakia oral	0/52 (0%)	0	3/49 (6.1%)	3	0/50 (0%)	0
Oral disorder	1/52 (1.9%)	1	0/49 (0%)	0	1/50 (2%)	1
Oral mucosal erythema	1/52 (1.9%)	1	1/49 (2%)	1	0/50 (0%)	0
Palatal disorder	0/52 (0%)	0	0/49 (0%)	0	2/50 (4%)	2
Dental discomfort	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Dry mouth	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Dyspepsia	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Gingival oedema	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Hypoaesthesia oral	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Lip haematoma	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Lip swelling	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Nausea	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Oral mucosal discolouration	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Oral mucosal exfoliation	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Oral pain	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Palatal swelling	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Paraesthesia oral	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Tongue discolouration	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Tongue disorder	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Tongue geographic	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Tongue ulceration	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Tooth loss	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Tooth resorption	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Traumatic occlusion	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
General disorders
Adverse drug reaction	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Chills	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Pyrexia	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Complication associated with device	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Hepatobiliary disorders
Cholecystitis	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Immune system disorders
Seasonal allergy	2/52 (3.8%)	2	0/49 (0%)	0	0/50 (0%)	0
Anaphylactic shock	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Hypersensitivity	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Infections and infestations
Nasopharyngitis	7/52 (13.5%)	7	4/49 (8.2%)	4	1/50 (2%)	1
Dental fistula	0/52 (0%)	0	1/49 (2%)	1	2/50 (4%)	2
Gastroenteritis viral	1/52 (1.9%)	1	0/49 (0%)	0	1/50 (2%)	1
Gingivitis	1/52 (1.9%)	1	1/49 (2%)	1	0/50 (0%)	0
Influenza	0/52 (0%)	0	1/49 (2%)	1	1/50 (2%)	1
Tooth abscess	0/52 (0%)	0	2/49 (4.1%)	2	0/50 (0%)	0
Urinary tract infection	2/52 (3.8%)	2	0/49 (0%)	0	0/50 (0%)	0
Angular cheilitis	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Arthritis bacterial	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Eye infection	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Gastroenteritis norovirus	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Kidney infection	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Lyme disease	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Oral herpes	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Pneumonia	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Sinusitis	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Tooth infection	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Vulvovaginal mycotic infection	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Injury, poisoning and procedural complications
Mouth injury	3/52 (5.8%)	3	2/49 (4.1%)	2	1/50 (2%)	1
Lip injury	3/52 (5.8%)	3	1/49 (2%)	1	1/50 (2%)	1
Tooth fracture	2/52 (3.8%)	2	1/49 (2%)	1	2/50 (4%)	2
Burn oral cavity	1/52 (1.9%)	1	1/49 (2%)	1	2/50 (4%)	2
Tongue injury	3/52 (5.8%)	3	0/49 (0%)	0	0/50 (0%)	0
Arthropod sting	1/52 (1.9%)	1	1/49 (2%)	1	0/50 (0%)	0
Thermal burn	0/52 (0%)	0	0/49 (0%)	0	2/50 (4%)	2
Arthropod bite	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Back injury	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Concussion	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Contusion	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Fall	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Gingival injury	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Laceration	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Muscle strain	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Post procedural swelling	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Procedural complication	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Procedural pain	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Investigations
Blood pressure increased	7/52 (13.5%)	7	5/49 (10.2%)	5	3/50 (6%)	3
Blood pressure systolic increased	2/52 (3.8%)	2	2/49 (4.1%)	2	0/50 (0%)	0
Blood pressure diastolic decreased	2/52 (3.8%)	2	0/49 (0%)	0	1/50 (2%)	1
Alanine aminotransferase increased	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Aspartate aminotransferase increased	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Blood pressure decreased	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Blood urine present	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
C-reactive protein increased	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Haemoglobin decreased	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Haemoglobin urine	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Lymphocyte count increased	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Mean cell volume increased	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Monocyte count decreased	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Neutrophil count decreased	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Protein urine present	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Red blood cell count decreased	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Urine leukocyte esterase positive	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
White blood cell count decreased	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Metabolism and nutrition disorders
Hypercholesterolaemia	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/52 (3.8%)	2	0/49 (0%)	0	0/50 (0%)	0
Muscle spasms	1/52 (1.9%)	1	1/49 (2%)	1	0/50 (0%)	0
Pain in jaw	0/52 (0%)	0	1/49 (2%)	1	1/50 (2%)	1
Arthralgia	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Arthritis	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Musculoskeletal pain	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Endometrial cancer	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Pancreatic carcinoma	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Nervous system disorders
Headache	1/52 (1.9%)	1	2/49 (4.1%)	2	1/50 (2%)	1
Dizziness	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Product Issues
Device failure	2/52 (3.8%)	2	1/49 (2%)	1	0/50 (0%)	0
Device damage	0/52 (0%)	0	0/49 (0%)	0	1/50 (2%)	1
Psychiatric disorders
Anxiety	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Reproductive system and breast disorders
Vaginal haemorrhage	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/52 (1.9%)	1	1/49 (2%)	1	0/50 (0%)	0
Lower respiratory tract congestion	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0
Hyperkeratosis	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Rash	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Rash pruritic	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Swelling face	0/52 (0%)	0	1/49 (2%)	1	0/50 (0%)	0
Vascular disorders
Hypertension	3/52 (5.8%)	3	0/49 (0%)	0	0/50 (0%)	0
Hypotension	1/52 (1.9%)	1	0/49 (0%)	0	0/50 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.