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Safety and Tolerability of Antiplaque Chewing Gum in a Gingivitis Population (APCG)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01877421
Recruitment Status : Completed
First Posted : June 13, 2013
Results First Posted : September 13, 2017
Last Update Posted : November 20, 2017
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Plaque
Gingivitis
Interventions Drug: 2 mg KSL-W
Drug: 4 mg KSL-W
Drug: 6 mg KSL-W
Drug: 10 mg KSL-W
Drug: 20 mg KSL-W
Drug: 30 mg KSL-W
Drug: 50 mg KSL-W
Drug: 75 mg KSL-W
Drug: 100 mg KSL-W
Other: Placebo
Enrollment 135
Recruitment Details There were a total of 137 planned subjects (71 in Phase 1 and 66 in Phase 2) to participate in this study at the Oral Health Research Institute, Indiana University School of Dentistry. There were a total of 135 enrolled (71 in Phase 1 and 64 in Phase 2). Phase 1 and 2 are individual periods ran in parallel.
Pre-assignment Details  
Arm/Group Title 2mg KSL-W 2mg Placebo 4mg KSL-W 4mg Placebo 6mg KSL-W 6mg Placebo 10mg KSL-W 10mg Placebo 20mg KSL-W 20mg Placebo 30mg KSL-W 30mg Placebo 50mg KSL-W 50mg Placebo 75mg KSL-W 75mg Placebo 100mg KSL-W 100mg Placebo
Hide Arm/Group Description 2mg KSL-W 2mg Placebo 4mg KSL-W 4mg Placebo 6mg KSL-W 6mg Placebo 10mg KSL-W 10mg Placebo 20mg KSL-W 20mg Placebo 30mg KSL-W 30mg Placebo 50mg KSL-W 50mg Placebo 75mg KSL-W 75mg Placebo 100mg KSL-W 100mg Placebo
Period Title: Phase 1
Started 2 1 4 2 4 2 4 2 7 3 7 3 7 3 7 3 7 3
Completed 2 1 4 2 4 2 4 2 7 3 7 3 7 3 7 3 7 3
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 2
Started 0 0 4 2 7 3 7 2 6 3 7 3 7 3 7 3 0 0
Completed 0 0 4 2 7 3 6 2 5 3 5 3 6 3 7 2 0 0
Not Completed 0 0 0 0 0 0 1 0 1 0 2 0 1 0 0 1 0 0
Reason Not Completed
Lost to Follow-up             0             0             0             0             0             0             1             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             0             0             1             0             1             0             1             0             0             1             0             0
Protocol Violation             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0
Arm/Group Title Phase 1, 1a (2mg) Phase 1, 1a Placebo Phase 1, 2a (4mg) Phase 1, 2a Placebo Phase 1, 3a (6mg) Phase 1, 3a Placebo Phase 1, 4a (10mg) Phase 1, 4a Placebo Phase 1, 5a (20mg) Phase 1, 5a Placebo Phase 1, 6a (30mg) Phase 1, 6a Placebo Phase 1, 7a (50mg) Phase 1, 7a Placebo Phase 1, 8a (75mg) Phase 1, 8a Placebo Phase 1, 9a (100mg) Phase 1, 9a Placebo Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo Total
Hide Arm/Group Description Subjects from phase 1, 1a (2mg) group Subjects from phase 1, 1a placebo group Subjects from phase 1, 2a (4mg) group Subjects from phase 1, 2a (4mg) group Subject from phase 1, 3a (6mg) group Subjects from phase 1, 3a placebo gorup Subjects from phase 1, 4a (10mg) group Subjects from phase 1, 4a placebo group Subjects from phase 1, 5a (20mg) group Subjects from phase1, 5a placebo group Subjects from phase 1, 6a (30mg) group Subjects from phase 1, 6a placebo group Subjects from phase 1, 7a (50mg) group Subjects from phase 1, 7a placebo group Subjects from phase 1, 8a (75mg) group Subjects from phase 1, 8a placebo group Subjects from phase 1, 9a (100mg) group Subjects from phase 1, 9a placebo group Subjects from phase 2, 1b (4mg) group Subjects from phase 2, 1b placebo Subjects from phase 2, 2b (6mg) group Subjects from phase 2, 2b placebo group Subjects from phase 2, 3b (10mg) group Subjects from phase 2, 3b placebo group Subjects from phase 2, 4b (20mg) group Subjects from phase 2, 4b placebo group Subjects from phase 2, 5b (30mg) group Subjects from phase 2, 5b placebo group Subjects from phase 2, 6b (50mg) group Subjects from phase 2, 6b placebo group Subjects from phase 2, 7b (75mg) group Subjects from phase 2, 7b placebo group Total of all reporting groups
Overall Number of Baseline Participants 2 1 4 2 4 2 4 2 7 3 7 3 7 3 7 3 7 3 4 2 7 3 7 2 6 3 7 3 7 3 7 3 135
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants 1 participants 4 participants 2 participants 4 participants 2 participants 4 participants 2 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 4 participants 2 participants 7 participants 3 participants 7 participants 2 participants 6 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 135 participants
45.5  (0.7) 49.0 [1]   (NA) 31.8  (5.5) 41.5  (2.1) 29.8  (5.1) 40.0  (5.7) 44.5  (5.0) 44.0  (11.3) 38.0  (14.3) 49.7  (9.5) 36.7  (8.9) 36.0  (5.6) 27.4  (7.5) 35.0  (19.1) 29.3  (6.7) 44.7  (13.6) 26.4  (10.4) 33.7  (20.6) 31.5  (11.4) 36.5  (16.3) 38.1  (12.2) 22.0  (3.6) 25.7  (5.8) 33.0  (15.6) 30.2  (14.3) 34.3  (13.6) 21.3  (4.8) 24.0  (5.0) 37.3  (13.9) 26.0  (10.4) 26.0  (5.0) 21.7  (0.6) 21.3  (0)
[1]
SD not derived because n=1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 1 participants 4 participants 2 participants 4 participants 2 participants 4 participants 2 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 4 participants 2 participants 7 participants 3 participants 7 participants 2 participants 6 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 135 participants
Female
2
 100.0%
1
 100.0%
3
  75.0%
1
  50.0%
2
  50.0%
0
   0.0%
0
   0.0%
1
  50.0%
4
  57.1%
1
  33.3%
5
  71.4%
3
 100.0%
6
  85.7%
3
 100.0%
5
  71.4%
3
 100.0%
5
  71.4%
2
  66.7%
1
  25.0%
0
   0.0%
5
  71.4%
1
  33.3%
1
  14.3%
1
  50.0%
3
  50.0%
1
  33.3%
2
  28.6%
2
  66.7%
5
  71.4%
2
  66.7%
3
  42.9%
2
  66.7%
76
  56.3%
Male
0
   0.0%
0
   0.0%
1
  25.0%
1
  50.0%
2
  50.0%
2
 100.0%
4
 100.0%
1
  50.0%
3
  42.9%
2
  66.7%
2
  28.6%
0
   0.0%
1
  14.3%
0
   0.0%
2
  28.6%
0
   0.0%
2
  28.6%
1
  33.3%
3
  75.0%
2
 100.0%
2
  28.6%
2
  66.7%
6
  85.7%
1
  50.0%
3
  50.0%
2
  66.7%
5
  71.4%
1
  33.3%
2
  28.6%
1
  33.3%
4
  57.1%
1
  33.3%
59
  43.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 1 participants 4 participants 2 participants 4 participants 2 participants 4 participants 2 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 4 participants 2 participants 7 participants 3 participants 7 participants 2 participants 6 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 135 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
  57.1%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
3
  42.9%
1
  33.3%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
13
   9.6%
Not Hispanic or Latino
2
 100.0%
1
 100.0%
4
 100.0%
2
 100.0%
3
  75.0%
2
 100.0%
4
 100.0%
2
 100.0%
3
  42.9%
3
 100.0%
6
  85.7%
3
 100.0%
7
 100.0%
3
 100.0%
7
 100.0%
2
  66.7%
4
  57.1%
2
  66.7%
3
  75.0%
2
 100.0%
7
 100.0%
3
 100.0%
7
 100.0%
2
 100.0%
6
 100.0%
3
 100.0%
7
 100.0%
3
 100.0%
7
 100.0%
3
 100.0%
6
  85.7%
3
 100.0%
122
  90.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 1 participants 4 participants 2 participants 4 participants 2 participants 4 participants 2 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 4 participants 2 participants 7 participants 3 participants 7 participants 2 participants 6 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 135 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  25.0%
1
  50.0%
0
   0.0%
1
  33.3%
1
  14.3%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  66.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
1
  50.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  14.3%
0
   0.0%
2
  28.6%
0
   0.0%
14
  10.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
 100.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
1
  14.3%
0
   0.0%
1
  14.3%
1
  33.3%
2
  28.6%
0
   0.0%
1
  25.0%
0
   0.0%
3
  42.9%
2
  66.7%
2
  28.6%
0
   0.0%
0
   0.0%
0
   0.0%
2
  28.6%
0
   0.0%
0
   0.0%
1
  33.3%
3
  42.9%
0
   0.0%
22
  16.3%
White
0
   0.0%
1
 100.0%
3
  75.0%
2
 100.0%
4
 100.0%
2
 100.0%
3
  75.0%
1
  50.0%
7
 100.0%
2
  66.7%
5
  71.4%
3
 100.0%
5
  71.4%
3
 100.0%
6
  85.7%
2
  66.7%
4
  57.1%
1
  33.3%
2
  50.0%
2
 100.0%
4
  57.1%
1
  33.3%
4
  57.1%
1
  50.0%
6
 100.0%
3
 100.0%
4
  57.1%
2
  66.7%
6
  85.7%
2
  66.7%
2
  28.6%
2
  66.7%
95
  70.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
4
   3.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants 1 participants 4 participants 2 participants 4 participants 2 participants 4 participants 2 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 4 participants 2 participants 7 participants 3 participants 7 participants 2 participants 6 participants 3 participants 7 participants 3 participants 7 participants 3 participants 7 participants 3 participants 135 participants
2 1 4 2 4 2 4 2 7 3 7 3 7 3 7 3 7 3 4 2 7 3 7 2 6 3 7 3 7 3 7 3 135
1.Primary Outcome
Title Safety and Tolerability of KSL-W as Measured by Soft Tissue Erythema, Ulceration and Sloughing (AEs and SAEs)
Hide Description Occurrence of local oral mucosal reactions, systemic reactions such as fever, nausea, headache, and changes in blood pressure, clinical laboratory measures of safety, and serious total body reactions will be assessed (AEs and SAEs)
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1, 1a (2mg) Phase 1, 1a Placebo Phase 1, 2a (4mg) Phase 1, 2a Placebo Phase 1, 3a (6mg) Phase 1, 3a Placebo Phase 1, 4a (10mg) Phase 1, 4a Placebo Phase 1, 5a (20mg) Phase 1, 5a Placebo Phase 1, 6a (30mg) Phase 1, 6a Placebo Phase 1, 7a (50mg) Phase 1, 7a Placebo Phase 1, 8a (75mg) Phase 1, 8a Placebo Phase 1, 9a (100mg) Phase 1, 9a Placebo Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Hide Arm/Group Description:
Subjects from phase 1, 1a (2mg) group
Subjects from phase 1, 1a placebo group
Subjects from phase 1, 2a (4mg) group
Subjects from phase 1, 2a (4mg) group
Subject from phase 1, 3a (6mg) group
Subjects from phase 1, 3a placebo gorup
Subjects from phase 1, 4a (10mg) group
Subjects from phase 1, 4a placebo group
Subjects from phase 1, 5a (20mg) group
Subjects from phase1, 5a placebo group
Subjects from phase 1, 6a (30mg) group
Subjects from phase 1, 6a placebo group
Subjects from phase 1, 7a (50mg) group
Subjects from phase 1, 7a placebo group
Subjects from phase 1, 8a (75mg) group
Subjects from phase 1, 8a placebo group
Subjects from phase 1, 9a (100mg) group
Subjects from phase 1, 9a placebo group
Subjects from phase 2, 1b (4mg) group
Subjects from phase 2, 1b placebo
Subjects from phase 2, 2b (6mg) group
Subjects from phase 2, 2b placebo group
Subjects from phase 2, 3b (10mg) group
Subjects from phase 2, 3b placebo group
Subjects from phase 2, 4b (20mg) group
Subjects from phase 2, 4b placebo group
Subjects from phase 2, 5b (30mg) group
Subjects from phase 2, 5b placebo group
Subjects from phase 2, 6b (50mg) group
Subjects from phase 2, 6b placebo group
Subjects from phase 2, 7b (75mg) group
Subjects from phase 2, 7b placebo group
Overall Number of Participants Analyzed 2 1 4 2 4 2 4 2 7 3 7 3 7 3 7 3 7 3 4 2 7 3 7 2 6 3 7 3 7 3 7 3
Measure Type: Count of Participants
Unit of Measure: Participants
Subject Experiencing AEs = NO
2
 100.0%
1
 100.0%
4
 100.0%
2
 100.0%
4
 100.0%
1
  50.0%
4
 100.0%
1
  50.0%
6
  85.7%
1
  33.3%
7
 100.0%
3
 100.0%
7
 100.0%
3
 100.0%
5
  71.4%
3
 100.0%
5
  71.4%
3
 100.0%
2
  50.0%
1
  50.0%
4
  57.1%
2
  66.7%
4
  57.1%
2
 100.0%
5
  83.3%
1
  33.3%
2
  28.6%
1
  33.3%
2
  28.6%
2
  66.7%
2
  28.6%
3
 100.0%
Subjects Experiencing AEs = YES
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  50.0%
0
   0.0%
1
  50.0%
1
  14.3%
2
  66.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  28.6%
0
   0.0%
2
  28.6%
0
   0.0%
2
  50.0%
1
  50.0%
3
  42.9%
1
  33.3%
3
  42.9%
0
   0.0%
1
  16.7%
2
  66.7%
5
  71.4%
2
  66.7%
5
  71.4%
1
  33.3%
5
  71.4%
0
   0.0%
2.Secondary Outcome
Title Proof of Concept of KSL-W in Reducing Plaque in Phase 2a
Hide Description

Data summarizes plaque index scores changes from baseline. Supragingival plaque will be assessed after the MGI and BOP assessments and following use of a disclosing solution on the facial (buccal) and lingual surfaces of a minimum of 16 scorable teeth according to the criteria of the Turesky modification of the Quigley-Hein Plaque Index.

Quigley-Hein Plaque Index Scores with Turesky Modifications:

0 No plaque

  1. Separate flecks of plaque at the cervical margin of the tooth
  2. A thin continuous band of plaque (up to one mm) at the cervical margin of the tooth
  3. A band of plaque wider than one mm but covering less than one-third of the crown of the tooth
  4. Plaque covering at least one-third but less than two thirds of the crown of the tooth
  5. Plaque covering two-thirds or more of the crown of the tooth
Time Frame days 14, 28, 34
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Hide Arm/Group Description:
Subjects from phase 2, 1b (4mg) group
Subjects from phase 2, 1b placebo
Subjects from phase 2, 2b (6mg) group
Subjects from phase 2, 2b placebo group
Subjects from phase 2, 3b (10mg) group
Subjects from phase 2, 3b placebo group
Subjects from phase 2, 4b (20mg) group
Subjects from phase 2, 4b placebo group
Subjects from phase 2, 5b (30mg) group
Subjects from phase 2, 5b placebo group
Subjects from phase 2, 6b (50mg) group
Subjects from phase 2, 6b placebo group
Subjects from phase 2, 7b (75mg) group
Subjects from phase 2, 7b placebo group
Overall Number of Participants Analyzed 4 2 7 3 7 2 5 3 6 3 7 3 7 3
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Whole Mouth: Day 14 0.20  (0.30) -0.06  (0.02) -0.12  (0.16) -0.10  (0.39) 0.01  (0.15) 0.04  (0.10) -0.08  (0.15) 0.01  (0.12) -0.31  (0.23) -0.14  (0.08) -0.52  (0.25) 0.06  (0.12) -0.53  (0.44) 0.28  (0.12)
Whole Mouth: Day 28 0.37  (0.42) -0.11  (0.07) -0.19  (0.10) 0.03  (0.08) 0.19  (0.21) 0.10  (0.10) -0.20  (0.09) 0.02  (0.15) -0.40  (0.36) -0.05  (0.03) -0.42  (0.20) 0.05  (0.15) -0.59  (0.54) 0.22  (0.11)
Whole Mouth: Day 34 0.22  (0.24) 0.00  (0.07) -0.17  (0.23) -0.16  (0.43) 0.25  (0.26) -0.01  (0.06) -0.08  (0.02) 0.00  (0.10) -0.21  (0.26) -0.04  (0.10) -0.18  (0.33) -0.17  (0.24) -0.20  (0.44) 0.49  (0.32)
Maxillary: Day 14 0.21  (0.44) -0.01  (0.11) -0.17  (0.21) -0.17  (0.40) -0.02  (0.21) -0.01  (0.14) -0.07  (0.24) 0.01  (0.15) -0.35  (0.31) -0.11  (0.09) -0.53  (0.27) 0.06  (0.10) -0.59  (0.52) 0.36  (0.03)
Maxillary: Day 28 0.41  (0.51) 0.03  (0.13) -0.19  (0.10) 0.01  (0.12) 0.13  (0.24) 0.06  (0.15) -0.22  (0.16) 0.08  (0.19) -0.49  (0.43) -0.03  (0.08) -0.38  (0.28) 0.06  (0.15) -0.56  (0.56) 0.24  (0.09)
Maxillary: Day 34 0.21  (0.31) 0.02  (0.19) -0.23  (0.20) -0.16  (0.32) 0.24  (0.25) -0.02  (0.01) -0.04  (0.07) 0.04  (0.12) -0.18  (0.35) -0.01  (0.13) -0.25  (0.34) -0.21  (0.26) -0.23  (0.50) 0.68  (0.31)
Mandibular: Day 14 0.19  (0.19) -0.13  (0.07) -0.07  (0.17) -0.02  (0.38) 0.014  (0.16) 0.09  (0.06) -0.09  (0.14) 0.00  (0.08) -0.27  (0.19) -0.17  (0.058) -0.50  (0.26) 0.06  (0.14) -0.48  (0.38) 0.20  (0.23)
Mandibular: Day 28 0.33  (0.36) -0.26  (0.27) -0.20  (0.21) 0.06  (0.06) 0.24  (0.21) 0.13  (0.05) -0.19  (0.05) -0.05  (0.24) -0.31  (0.31) -0.07  (0.07) -0.46  (0.20) 0.04  (0.17) -0.62  (0.53) 0.19  (0.12)
Mandibular: Day 34 0.24  (0.174) -0.03  (0.05) -0.11  (0.28) -0.16  (0.54) 0.26  (0.30) 0.00  (0.12) -0.11  (0.04) -0.04  (0.15) -0.23  (0.18) -0.07  (0.12) -0.12  (0.32) -0.14  (0.22) -0.17  (0.38) 0.30  (0.32)
Posterior: Day 14 0.14  (0.26) -0.04  (0.09) -0.20  (0.22) 0.08  (0.16) -0.06  (0.15) 0.00  (0.31) -0.10  (0.14) 0.09  (0.07) -0.45  (0.33) -0.22  (0.14) -0.66  (0.30) 0.04  (0.18) -0.60  (0.44) 0.31  (0.17)
Posterior: Day 28 0.39  (0.34) -0.18  (0.05) -0.30  (0.13) 0.08  (0.06) 0.09  (0.20) 0.05  (0.15) -0.25  (0.10) 0.03  (0.21) -0.58  (0.44) -0.14  (0.14) -0.52  (0.19) 0.04  (0.16) -0.69  (0.54) 0.22  (0.16)
Posterior: Day 34 0.27  (0.15) 0.00  (0.09) -0.24  (0.22) 0.08  (0.23) 0.24  (0.24) -0.03  (0.10) -0.10  (0.07) 0.06  (0.19) -1.31  (0.31) -0.07  (0.15) -0.18  (0.39) -0.21  (0.37) -0.18  (0.40) 0.53  (0.37)
Interproximal: Day 14 0.25  (0.31) 0.02  (0.15) -0.12  (0.24) -0.10  (0.36) 0.09  (0.19) 0.06  (0.04) -0.08  (0.11) 0.03  (0.08) -0.36  (0.33) -0.20  (0.08) 0.61  (0.29) 0.04  (0.18) -0.58  (0.49) 0.32  (0.08)
Interproximal: Day 28 0.41  (0.46) -0.08  (0.06) -0.20  (0.13) -0.03  (0.07) 0.28  (0.28) 0.12  (0.05) -0.22  (0.12) -0.02  (0.09) -0.60  (0.39) -0.21  (0.07) -0.53  (0.25) 0.02  (0.10) -0.67  (0.61) 0.24  (0.20)
Interproximal: Day 34 0.30  (0.21) 0.06  (0.08) -0.18  (0.27) -0.16  (0.41) 0.37  (0.34) -0.01  (0.12) -0.07  (0.05) -0.06  (0.03) -0.24  (0.28) -0.05  (0.11) -0.24  (0.43) -0.21  (0.24) -0.18  (0.44) 0.54  (0.40)
Facial: Day 14 0.30  (0.47) -0.17  (0.04) -0.08  (0.24) -0.09  (0.47) 0.07  (0.18) 0.03  (0.16) -0.06  (0.17) -0.02  (0.19) -0.20  (0.28) -0.06  (0.21) -0.45  (0.37) 0.10  (0.03) -0.60  (0.55) 0.31  (0.17)
Facial: Day 28 0.52  (0.65) -0.20  (0.03) -0.18  (0.20) 0.11  (0.10) 0.24  (0.29) 0.02  (0.13) -0.08  (0.10) 0.06  (0.21) -0.16  (0.43) 0.07  (0.14) -0.37  (0.36) -0.03  (0.23) -0.70  (0.69) 0.29  (0.20)
Facial: Day 34 0.25  (0.44) -0.14  (0.16) -0.12  (0.29) -0.16  (0.54) 0.28  (0.40) -0.12  (0.04) -0.05  (0.08) 0.03  (0.08) -0.08  (0.41) -0.04  (0.09) -0.17  (0.36) -0.22  (0.29) -0.25  (0.60) 0.57  (0.35)
Lingual: Day 14 0.10  (0.14) 0.04  (0.09) -0.16  (0.19) 0.11  (0.31) -0.05  (0.15) 0.06  (0.04) -0.10  (0.21) 0.03  (0.05) -0.43  (0.26) -0.22  (0.10) -0.59  (0.23) 0.03  (0.21) -0.47  (0.41) 0.25  (0.08)
Lingual: Day 28 0.22  (0.24) -0.02  (0.10) -0.20  (0.19) -0.06  (0.11) 0.14  (0.23) 0.17  (0.07) -0.32  (0.18) -0.02  (0.11) -0.64  (0.41) -0.16  (0.17) -0.47  (0.17) 0.13  (0.10) -0.48  (0.40) 0.15  (0.01)
Lingual: Day 34 0.20  (0.08) 0.14  (0.02) -0.22  (0.28) -0.16  (0.32) 0.22  (0.26) 0.10  (0.08) -0.11  (0.11) -0.02  (0.12) -0.33  (0.13) -0.03  (0.16) -0.20  (0.34) -0.12  (0.18) -0.14  (0.32) 0.42  (0.29)
3.Secondary Outcome
Title Proof of Concept of KSL-W in Reducing Gingivitis in Phase 2a
Hide Description

Data summarizes gingival index scores changes from baseline in phase 2a. Gingivitis will be assessed using both the MGI (Modified Gingival Index) and the Gingival Bleeding Index (BOP) The Modified Gingival Index assesses the buccal and lingual gingivae and interdental papillae.

Modified Gingival Index Scores:

0 Absence of inflammation

  1. Mild inflammation; slight change in color, little change in texture of any portion of but not the entire marginal or papillary gingival unit
  2. Mild inflammation; criteria as above but involving the entire marginal or papillary gingival unit
  3. Moderate inflammation; glazing, redness, edema and/or hypertrophy of the marginal or papillary gingival unit
  4. Severe inflammation; marked redness, edema and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration.
Time Frame days 14, 28, 34
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Hide Arm/Group Description:
Subjects from phase 2, 1b (4mg) group
Subjects from phase 2, 1b placebo
Subjects from phase 2, 2b (6mg) group
Subjects from phase 2, 2b placebo group
Subjects from phase 2, 3b (10mg) group
Subjects from phase 2, 3b placebo group
Subjects from phase 2, 4b (20mg) group
Subjects from phase 2, 4b placebo group
Subjects from phase 2, 5b (30mg) group
Subjects from phase 2, 5b placebo group
Subjects from phase 2, 6b (50mg) group
Subjects from phase 2, 6b placebo group
Subjects from phase 2, 7b (75mg) group
Subjects from phase 2, 7b placebo group
Overall Number of Participants Analyzed 4 2 7 3 7 2 5 3 6 3 7 3 7 3
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Whole Mouth: Day 14 -0.03  (0.05) -0.06  (0.09) 0.00  (0.04) 0.14  (0.10) 0.04  (0.11) 0.10  (0.04) 0.01  (0.03) 0.05  (0.03) -0.11  (0.08) -0.12  (0.09) -0.03  (0.12) 0.00  (0.18) -0.10  (0.11) 0.00  (0.07)
Whole Mouth: Day 28 0.10  (0.06) 0.04  (0.02) 0.00  (0.07) 0.06  (0.10) 0.03  (0.12) 0.14  (0.07) 0.07  (0.03) 0.08  (0.13) -0.13  (0.06) -0.09  (0.13) -0.02  (0.09) -0.11  (0.11) -0.10  (0.08) 0.12  (0.10)
Whole Mouth: Day 34 0.05  (0.10) 0.02  (0.08) -0.01  (0.09) 0.06  (0.04) -0.05  (0.08) 0.02  (0.08) 0.04  (0.04) -0.03  (0.09) -0.15  (0.04) 0.13  (0.08) -0.04  (0.07) -0.08  (0.09) -0.05  (0.08) 0.16  (0.00)
Maxillary: Day 14 -0.06  (0.03) -0.08  (0.10) 0.01  (0.10) 0.15  (0.13) 0.02  (0.14) 0.11  (0.05) 0.00  (0.09) -0.02  (0.05) -0.11  (0.08) -0.05  (0.08) -0.03  (0.19) -0.04  (0.25) -0.17  (0.11) 0.02  (0.04)
Maxillary: Day 28 0.01  (0.06) 0.04  (0.07) 0.00  (0.14) 0.01  (0.19) 0.06  (0.17) 0.09  (0.09) 0.08  (0.05) 0.03  (0.19) -0.12  (0.07) -0.03  (0.18) 0.00  (0.11) -0.15  (0.16) -0.12  (0.09) 0.15  (0.06)
Maxillary: Day 34 -0.02  (0.12) 0.00  (0.07) -0.02  (0.15) 0.01  (0.16) -0.03  (0.16) -0.02  (0.06) 0.01  (0.09) -0.09  (0.14) -0.15  (0.08) -0.09  (0.11) -0.06  (0.05) -0.12  (0.09) -0.12  (0.08) 0.16  (0.09)
Mandibular: Day 14 0.00  (0.09) -0.03  (0.09) 0.00  (0.08) 0.12  (0.18) 0.07  (0.09) 0.10  (0.03) 0.01  (0.05) 0.13  (0.07) -0.10  (0.10) -0.19  (0.11) -0.02  (0.07) 0.03  (0.10) -0.02  (0.13) -0.02  (0.12)
Mandibular: Day 28 0.18  (0.08) 0.05  (0.03) -0.01  (0.11) 0.11  (0.06) 0.00  (0.08) 0.19  (0.05) 0.05  (0.05) 0.12  (0.07) -0.14  (0.06) -0.15  (0.07) -0.04  (0.12) -0.07  (0.10) -0.07  (0.09) 0.10  (0.13)
Mandibular: Day 34 0.13  (0.09) 0.05  (0.08) 0.01  (0.047) 0.10  (0.09) -0.06  (0.07) 0.07  (0.11) 0.07  (0.06) 0.03  (0.08) -0.14  (0.11) -0.17  (0.07) -0.01  (0.13) -0.04  (0.12) 0.01  (0.10) 0.17  (0.08)
Posterior: Day 14 0.00  (0.04) -0.05  (0.07) 0.00  (0.11) 0.10  (0.11) 0.05  (0.11) 0.11  (0.10) -0.01  (0.02) 0.03  (0.04) -0.11  (0.12) -0.10  (0.15) 0.00  (0.11) 0.01  (0.14) -0.11  (0.10) 0.00  (0.05)
Posterior: Day 28 0.17  (0.10) 0.02  (0.02) 0.01  (0.07) 0.06  (0.11) 0.02  (0.11) 0.19  (0.07) 0.12  (0.05) 0.10  (0.08) -0.10  (0.06) -0.12  (0.19) 0.04  (0.10) -0.12  (0.14) -0.11  (0.10) 0.08  (0.05)
Posterior: Day 34 0.06  (0.09) 0.09  (0.01) -0.02  (0.14) 0.06  (0.04) -0.03  (0.06) 0.08  (0.15) 0.06  (0.05) -0.04  (0.07) -0.13  (0.11) -0.14  (0.14) -0.03  (0.07) -0.09  (0.05) -0.08  (0.06) 0.15  (0.01)
Interproximal: Day 14 -0.03  (0.05) -0.06  (0.09) 0.02  (0.06) 0.12  (0.11) 0.04  (0.10) 0.09  (0.01) 0.00  (0.02) 0.08  (0.08) -0.10  (0.10) -0.08  (0.08) -0.01  (0.13) -0.01  (0.19) -0.11  (0.13) -0.06  (0.07)
Interproximal: Day 28 0.02  (0.06) 0.01  (0.06) 0.03  (0.03) 0.05  (0.08) 0.04  (0.10) 0.16  (0.03) 0.07  (0.06) 0.10  (0.11) -0.14  (0.06) -0.05  (0.13) 0.01  (0.08) -0.10  (0.15) -0.11  (0.09) 0.08  (0.14)
Interproximal: Day 34 0.02  (0.11) 0.02  (0.04) 0.01  (0.08) 0.05  (0.02) -0.06  (0.07) 0.01  (0.09) 0.03  (0.05) 0.00  (0.12) -0.15  (0.05) -0.09  (0.05) -0.02  (0.07) -0.08  (0.10) -0.07  (0.09) 0.18  (0.03)
Facial: Day 14 0.04  (0.10) -0.05  (0.14) -0.04  (0.11) 0.10  (0.09) 0.02  (0.13) 0.05  (0.08) 0.00  (0.03) 0.05  (0.09) -0.08  (0.05) -0.09  (0.14) -0.06  (0.15) 0.04  (0.22) -0.05  (0.09) -0.05  (0.08)
Facial: Day 28 0.19  (0.14) 0.02  (0.03) 0.00  (0.09) 0.08  (0.08) 0.01  (0.13) 0.16  (0.04) 0.09  (0.09) 0.10  (0.00) -0.11  (0.08) -0.06  (0.17) -0.05  (0.12) -0.11  (0.15) -0.07  (0.06) 0.09  (0.08)
Facial: Day 34 0.09  (0.16) -0.05  (0.09) -0.02  (0.15) 0.10  (0.047) -0.04  (0.08) -0.05  (0.02) 0.01  (0.07) -0.07  (0.14) -0.12  (0.03) -0.10  (0.09) -0.06  (0.09) -0.09  (0.12) -0.04  (0.07) 0.19  (0.00)
Lingual: Day 14 -0.10  (0.10) -0.06  (0.05) 0.05  (0.10) 0.18  (0.12) 0.06  (0.14) 0.15  (0.15) 0.01  (0.06) 0.06  (0.07) -0.13  (0.13) -0.15  (0.04) 0.00  (0.10) -0.05  (0.14) -0.14  (0.16) 0.05  (0.07)
Lingual: Day 28 0.00  (0.09) 0.07  (0.01) 0.00  (0.07) 0.03  (0.13) 0.05  (0.14) 0.12  (0.19) 0.05  (0.08) 0.06  (0.25) -0.15  (0.06) -0.12  (0.08) 0.01  (0.10) -0.12  (0.08) -0.13  (0.11) 0.15  (0.12)
Lingual: Day 34 0.01  (0.07) 0.10  (0.07) 0.00  (0.09) 0.02  (0.16) -0.05  (0.14) 0.10  (0.15) 0.08  (0.06) 0.01  (0.04) -0.17  (0.07) -0.17  (0.08) -0.01  (0.07) -0.07  (0.07) -0.06  (0.14) 0.14  (0.01)
4.Secondary Outcome
Title Gingival Bleeding on Probing (BOP) - Percent of Bleeding Sites Upon Probing in Phase 2a
Hide Description

Proof of concept of KSL-W in reducing plaque as measured by percent of bleeding sites upon probing (BOP) in phase 2a.

Gingivitis will be assessed using both the MGI (Modified Gingival Index) and the Gingival Bleeding Index (BOP). The Modified Gingival Index assesses the buccal and lingual gingivae and interdental papillae. The Gingival Bleeding Index assesses the percentage of sites that bleed on gentle probing. A periodontal probe (HU-Friedy UNC 15) will be gently inserted into the gingival sulcus until resistance is felt at mid-facial (buccal), mid-lingual, mesial, and distal interproximal sites of all scorable teeth, with the exception of the most posterior distal sites. Presence or absence of bleeding will be recorded for each site and the percentage of bleeding sites per subject will serve as the unit of analysis.

Time Frame days 0, 14, 28, 34
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Hide Arm/Group Description:
Subjects from phase 2, 1b (4mg) group
Subjects from phase 2, 1b placebo
Subjects from phase 2, 2b (6mg) group
Subjects from phase 2, 2b placebo group
Subjects from phase 2, 3b (10mg) group
Subjects from phase 2, 3b placebo group
Subjects from phase 2, 4b (20mg) group
Subjects from phase 2, 4b placebo group
Subjects from phase 2, 5b (30mg) group
Subjects from phase 2, 5b placebo group
Subjects from phase 2, 6b (50mg) group
Subjects from phase 2, 6b placebo group
Subjects from phase 2, 7b (75mg) group
Subjects from phase 2, 7b placebo group
Overall Number of Participants Analyzed 4 2 7 3 7 2 6 3 7 3 7 3 7 3
Mean (Standard Deviation)
Unit of Measure: Percent of bleeding sites
Whole Mouth: Eligibility 16  (15) 27  (26) 26  (10) 22  (16) 17  (16) 27  (7) 30  (14) 37  (26) 25  (8) 17  (5) 20  (15) 19  (8) 13  (9) 11  (9)
Whole Mouth: Day 0 20  (12) 37  (31) 29  (12) 19  (6) 16  (11) 26  (5) 29  (19) 38  (28) 31  (14) 19  (8) 25  (19) 27  (12) 21  (16) 17  (4)
Whole Mouth: Day 14 16  (15) 28  (24) 21  (11) 24  (13) 17  (15) 15  (11) 25  (17) 33  (20) 24  (14) 20  (14) 19  (8) 32  (1) 15  (7) 15  (9)
Whole Mouth: Day 28 16  (18) 24  (29) 25  (9) 23  (14) 13  (10) 25  (12) 33  (21) 28  (8) 25  (16) 24  (3) 17  (17) 31  (18) 22  (9) 13  (1)
Whole Mouth: Day 34 18  (18) 46  (11) 18  (10) 22  (15) 16  (12) 28  (27) 31  (17) 31  (21) 22  (13) 12  (6) 10  (5) 24  (14) 19  (10) 20  (4)
Maxillary: Eligibility 16  (18) 26  (25) 26  (11) 29  (15) 17  (15) 29  (14) 33  (20) 37  (22) 26  (12) 17  (8) 23  (20) 16  (3) 14  (8) 8  (5)
Maxillary: Day 0 24  (19) 30  (29) 27  (11) 21  (3) 17  (12) 21  (2) 31  (28) 37  (23) 29  (13) 20  (11) 32  (24) 22  (11) 22  (17) 20  (6)
Maxillary: Day 14 19  (25) 30  (29) 21  (16) 33  (15) 19  (16) 12  (2) 29  (21) 33  (15) 26  (17) 16  (12) 24  (12) 36  (7) 14  (12) 15  (6)
Maxillary: Day 28 14  (14) 26  (29) 25  (10) 27  (17) 15  (13) 21  (14) 31  (23) 30  (10) 231  (16) 26  (5) 18  (17) 30  (21) 24  (12) 15  (4)
Maxillary: Day 34 22  (26) 39  (11) 19  (13) 25  (15) 15  (10) 26  (27) 28  (18) 29  (17) 22  (13) 13  (10) 11  (3) 24  (14) 18  (9) 17  (2)
Mandibular: Eligibility 16  (12) 28  (28) 26  (12) 15  (18) 17  (18) 26  (1) 27  (12) 36  (30) 24  (7) 17  (5) 16  (12) 22  (14) 11  (11) 15  (13)
Mandibular: Day 0 17  (6) 43  (32) 31  (15) 18  (14) 15  (11) 32  (8) 26  (13) 39  (34) 32  (17) 17  (7) 18  (14) 33  (16) 20  (17) 13  (3)
Mandibular: Day 14 13  (8) 27  (19) 20  (10) 16  (13) 16  (15) 18  (21) 21  (14) 34  (28) 22  (15) 25  (17) 15  (6) 28  (6) 17  (12) 15  (12)
Mandibular: Day 28 17  (22) 23  (29) 25  (12) 19  (12) 12  (9) 29  (10) 34  (20) 27  (8) 28  (17) 22  (2) 17  (17) 32  (17) 19  (12) 11  (3)
Mandibular: Day 34 15  (11) 52  (10) 17  (10) 18  (16) 16  (15) 30  (26) 34  (18) 34  (26) 22  (15) 10  (4) 9  (12) 25  (14) 21  (15) 23  (9)
Posterior: Eligibility 21  (21) 24  (23) 30  (12) 28  (10) 21  (19) 29  (13) 34  (16) 36  (17) 25  (9) 19  (6) 22  (16) 21  (10) 14  (11) 12  (6)
Posterior: Day 0 25  (11) 40  (32) 32  (15) 22  (5) 20  (13) 33  (5) 30  (19) 38  (25) 32  (15) 20  (6) 27  (21) 34  (16) 24  (21) 19  (7)
Posterior: Day 14 19  (20) 32  (26) 26  (15) 34  (9) 23  (19) 17  (7) 28  (16) 35  (17) 27  (14) 19  (9) 23  (9) 39  (3) 17  (7) 16  (12)
Posterior: Day 28 20  (24) 26  (29) 29  (9) 30  (17) 17  (14) 30  (21) 34  (22) 30  (10) 24  (15) 27  (4) 20  (19) 34  (20) 24  (10) 14  (0)
Posterior: Day 34 22  (21) 45  (18) 23  (9) 26  (10) 19  (14) 31  (32) 32  (16) 33  (21) 24  (14) 13  (6) 13  (5) 27  (13) 20  (12) 27  (7)
Interproximal: Eligibility 21  (19) 32  (32) 32  (12) 30  (23) 20  (19) 38  (9) 37  (18) 44  (29) 30  (9) 21  (4) 24  (18) 22  (8) 16  (10) 14  (10)
Interproximal: Day 0 25  (14) 39  (28) 36  (15) 24  (8) 19  (13) 34  (4) 34  (21) 45  (33) 36  (17) 21  (8) 29  (20) 33  (15) 24  (19) 20  (7)
Interproximal: Day 14 20  (20) 34  (26) 26  (14) 32  (17) 20  (18) 20  (14) 31  (22) 39  (23) 28  (17) 25  (22) 23  (11) 36  (3) 17  (8) 17  (11)
Interproximal: Day 28 19  (21) 29  (32) 32  (11) 31  (20) 16  (11) 30  (13) 38  (26) 35  (8) 26  (16) 29  (5) 20  (22) 32  (20) 25  (11) 16  (3)
Interproximal: Day 34 23  (21) 54  (10) 22  (11) 27  (18) 19  (14) 34  (30) 37  (19) 36  (25) 25  (15) 14  (9) 10  (7) 27  (14) 23  (11) 25  (3)
Facial: Eligibility 15  (14) 35  (36) 22  (11) 17  (10) 11  (7) 29  (4) 24  (11) 35  (21) 22  (14) 17  (3) 16  (13) 17  (13) 10  (11) 10  (11)
Facial: Day 0 16  (9) 39  (39) 28  (13) 16  (5) 10  (7) 20  (4) 22  (16) 35  (28) 31  (17) 11  (5) 25  (19) 25  (14) 22  (18) 12  (7)
Facial: Day 14 16  (13) 37  (37) 19  (11) 29  (10) 11  (10) 17  (8) 19  (13) 34  (13) 23  (18) 19  (15) 19  (10) 29  (9) 12  (8) 11  (5)
Facial: Day 28 12  (13) 27  (34) 22  (9) 20  (16) 5  (4) 23  (15) 23  (19) 23  (10) 23  (18) 22  (5) 13  (13) 27  (28) 16  (11) 6  (0)
Facial: Day 34 14  (16) 46  (17) 15  (9) 15  (16) 11  (7) 21  (19) 24  (13) 27  (16) 22  (19) 10  (4) 8  (4) 22  (18) 16  (12) 18  (11)
Lingual: Eligibility 16  (18) 18  (16) 30  (12) 26  (23) 24  (27) 26  (9) 36  (19) 38  (32) 28  (8) 17  (8) 23  (19) 21  (5) 16  (9) 13  (7)
Lingual: Day 0 25  (19) 34  (22) 29  (15) 23  (7) 22  (16) 33  (5) 35  (23) 41  (29) 30  (14) 27  (13) 25  (20) 30  (14) 21  (14) 22  (1)
Lingual: Day 14 16  (18) 19  (11) 22  (13) 20  (15) 23  (21) 14  (14) 31  (22) 33  (31) 25  (13) 21  (15) 20  (9) 35  (6) 19  (8) 19  (13)
Lingual: Day 28 19  (23) 21  (24) 28  (13) 27  (13) 22  (17) 27  (9) 42  (26) 33  (13) 26  (15) 25  (7) 22  (23) 35  (10) 258  (8) 20  (2)
Lingual: Day 34 23  (21) 45  (4) 20  (15) 28  (16) 21  (20) 36  (34) 39  (22) 36  (28) 21  (8) 13  (8) 11  (8) 27  (11) 23  (10) 21  (3)
Time Frame up to 28 days
Adverse Event Reporting Description Formal statistical analysis of the safety data was not performed due to the small sample size.
 
Arm/Group Title Phase 1, 1a (2mg) Phase 1, 1a Placebo Phase 1, 2a (4mg) Phase 1, 2a Placebo Phase 1, 3a (6mg) Phase 1, 3a Placebo Phase 1, 4a (10mg) Phase 1, 4a Placebo Phase 1, 5a (20mg) Phase 1, 5a Placebo Phase 1, 6a (30mg) Phase 1, 6a Placebo Phase 1, 7a (50mg) Phase 1, 7a Placebo Phase 1, 8a (75mg) Phase 1, 8a Placebo Phase 1, 9a (100mg) Phase 1, 9a Placebo Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Hide Arm/Group Description Subjects from phase 1, 1a (2mg) group Subjects from phase 1, 1a placebo group Subjects from phase 1, 2a (4mg) group Subjects from phase 1, 2a (4mg) group Subject from phase 1, 3a (6mg) group Subjects from phase 1, 3a placebo gorup Subjects from phase 1, 4a (10mg) group Subjects from phase 1, 4a placebo group Subjects from phase 1, 5a (20mg) group Subjects from phase1, 5a placebo group Subjects from phase 1, 6a (30mg) group Subjects from phase 1, 6a placebo group Subjects from phase 1, 7a (50mg) group Subjects from phase 1, 7a placebo group Subjects from phase 1, 8a (75mg) group Subjects from phase 1, 8a placebo group Subjects from phase 1, 9a (100mg) group Subjects from phase 1, 9a placebo group Subjects from phase 2, 1b (4mg) group Subjects from phase 2, 1b placebo Subjects from phase 2, 2b (6mg) group Subjects from phase 2, 2b placebo group Subjects from phase 2, 3b (10mg) group Subjects from phase 2, 3b placebo group Subjects from phase 2, 4b (20mg) group Subjects from phase 2, 4b placebo group Subjects from phase 2, 5b (30mg) group Subjects from phase 2, 5b placebo group Subjects from phase 2, 6b (50mg) group Subjects from phase 2, 6b placebo group Subjects from phase 2, 7b (75mg) group Subjects from phase 2, 7b placebo group
All-Cause Mortality
Phase 1, 1a (2mg) Phase 1, 1a Placebo Phase 1, 2a (4mg) Phase 1, 2a Placebo Phase 1, 3a (6mg) Phase 1, 3a Placebo Phase 1, 4a (10mg) Phase 1, 4a Placebo Phase 1, 5a (20mg) Phase 1, 5a Placebo Phase 1, 6a (30mg) Phase 1, 6a Placebo Phase 1, 7a (50mg) Phase 1, 7a Placebo Phase 1, 8a (75mg) Phase 1, 8a Placebo Phase 1, 9a (100mg) Phase 1, 9a Placebo Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)      0/1 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/2 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1, 1a (2mg) Phase 1, 1a Placebo Phase 1, 2a (4mg) Phase 1, 2a Placebo Phase 1, 3a (6mg) Phase 1, 3a Placebo Phase 1, 4a (10mg) Phase 1, 4a Placebo Phase 1, 5a (20mg) Phase 1, 5a Placebo Phase 1, 6a (30mg) Phase 1, 6a Placebo Phase 1, 7a (50mg) Phase 1, 7a Placebo Phase 1, 8a (75mg) Phase 1, 8a Placebo Phase 1, 9a (100mg) Phase 1, 9a Placebo Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/2 (0.00%)      0/1 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/2 (0.00%)      0/6 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1, 1a (2mg) Phase 1, 1a Placebo Phase 1, 2a (4mg) Phase 1, 2a Placebo Phase 1, 3a (6mg) Phase 1, 3a Placebo Phase 1, 4a (10mg) Phase 1, 4a Placebo Phase 1, 5a (20mg) Phase 1, 5a Placebo Phase 1, 6a (30mg) Phase 1, 6a Placebo Phase 1, 7a (50mg) Phase 1, 7a Placebo Phase 1, 8a (75mg) Phase 1, 8a Placebo Phase 1, 9a (100mg) Phase 1, 9a Placebo Phase 2, 1b (4mg) Phase 2, 1b Placebo Phase 2, 2b (6mg) Phase 2, 2b Placebo Phase 2, 3b (10mg) Phase 2, 3b Placebo Phase 2, 4b (20mg) Phase 2, 4b Placebo Phase 2, 5b (30mg) Phase 2, 5b Placebo Phase 2, 6b (50mg) Phase 2, 6b Placebo Phase 2, 7b (75mg) Phase 2, 7b Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/2 (0.00%)      0/1 (0.00%)      0/4 (0.00%)      0/2 (0.00%)      0/4 (0.00%)      1/2 (50.00%)      0/4 (0.00%)      1/2 (50.00%)      1/7 (14.29%)      2/3 (66.67%)      0/7 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)      2/7 (28.57%)      0/3 (0.00%)      2/7 (28.57%)      0/3 (0.00%)      2/4 (50.00%)      1/2 (50.00%)      3/7 (42.86%)      1/3 (33.33%)      3/7 (42.86%)      0/2 (0.00%)      1/6 (16.67%)      2/3 (66.67%)      5/7 (71.43%)      2/3 (66.67%)      5/7 (71.43%)      1/3 (33.33%)      5/7 (71.43%)      0/3 (0.00%)    
Ear and labyrinth disorders                                                                 
Vertigo * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal disorders                                                                 
Abdominal discomfort * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0
Abdominal discomfort  1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Coating in mouth * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0
Device connection issue * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Dyspepsia * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Dyspepsia  1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Erythema, hard palate, right side, molar area * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Flatulence  1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Food poisoning * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Abdomin discomfort, upper stomach  1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Gingival ulceration * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Mouth haemorrhage * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Mouth ulceration * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Oral mucosal erythema * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Oral mucosal erythema  1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Oral pain  1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Puffy and wrinkling sensation, bilateral buccal mucosa * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Teeth staining * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Tongue coated * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 3/7 (42.86%)  3 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Tongue pigmentation * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0
Toothh discoloration * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 2/7 (28.57%)  2 0/3 (0.00%)  0
Infections and infestations                                                                 
Ear infection * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/2 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Nasopharyngitis * 1  0/2 (0.00%)  0 0/1 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/4 (0.00%)  0 0/2 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0