Gingival Inflammation
Conditions
Keywords
Safety and efficacy of BLXA4
Brief summary
The primary objective is to evaluate the safety of an investigational compound, BLXA4-ME, topically applied as a daily oral rinse in adults with gingivitis. Safety will be assessed by the incidence of adverse events, including mucosal inflammation and irritancy and findings from safety labs. Subjects will be monitored for development of periodontitis, and oral flora will be analyzed to detect an increase in opportunistic organisms. The secondary objective is to assess preliminary efficacy of the oral rinse, by monitoring changes in the plaque index (PI), modified gingival index (MGI), bleeding on probing (BOP) and levels of interleukin -1β (IL-1β) in gingival crevicular fluid (GCF). The study comprises three groups in a randomized, placebo-controlled double-blind clinical trial design. The treatment group (1.0 μM BLXA4-ME oral rinse) and the placebo rinse group will each include 50 subjects. The no-rinse control group will consist of 25 subjects. Subjects in the treatment and placebo rinse groups will receive oral rinse (BLXA4-ME or placebo) to be applied once daily after morning teeth brushing. Safety parameters will be assessed before and after 3, 7, 14, 21, and 28 days of treatment. Efficacy parameters will be assessed before and after 14 and 28 days of treatment.
Interventions
DRUGBLXA4
BLXA4-ME is a member of a new class of chemically and metabolically stable lipoxin analogs featuring a replacement of the tetraene unit of native lipoxin-A4 (LXA4) with a substituted benzo-fused ring system. The full chemical name of the BLXA4-ME drug substance is (5S, 6R, E)-methyl 5,6-dihydroxy-8-(2-((R,E)-3-hydroxyoct-1-enyl) phenyl) oct-7-enoate.
The placebo preparation will consist of formulated oral rinse without BLXA4-ME and will be identical to the test rinse in color, appearance and taste
Sponsors
National Institute of Dental and Craniofacial Research (NIDCR)
The Forsyth Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed consent form * Good general health as evidenced by medical history * Age 18 - 65 * Must have a stable address and be available for the duration of the study * Must have a minimum of 20 natural teeth, excluding third molars * Must have a mean full mouth MGI of at least 2.0 * Must be willing to use prescribed oral hygiene procedures and products * Medications for chronic conditions must be stable for at least 3 months prior to enrollment * Women of reproductive potential must use licensed hormonal contraception or double barrier methods * Men of reproductive potential must agree to use condoms * Liver function test (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, and total bilirubin) levels equal to or less than 1.5 times the upper limit of normal * Serum creatinine levels equal to or less than the upper limit of normal; * Subjects with complete blood count levels within 10% of the normal laboratory range and erythrocyte sedimentation rate equal to or less than 2 times the upper limit of normal.
Exclusion criteria
* Presence of orthodontic appliances or removable partial dentures * Presence of a soft tissue tumor of the oral cavity * Presence of gross plaque or calculus (≥ 75% of tooth surfaces) * Presence of extensive restorations that could affect the marginal gingiva (at the investigators' discretion) * Preexisting oral pathology, including carious lesions requiring immediate treatment or ulcerations of the mucosa * Current participation in another clinical trial or product test * Pregnant or breast feeding * Residence in the same household as a subject currently enrolled in the study (due to potential blinding and compliance issues) * Concomitant endodontic therapy or periodontal therapy other than prophylaxis within the past 6 months * History of early onset periodontitis or acute necrotizing ulcerative gingivitis * Chronic disease with concomitant oral manifestations, such as autoimmune or immunosuppressive diseases (e.g., human immunodeficiency virus, severe combined immunodeficiency, neutropenia, juvenile arthritis, systemic lupus erythematosus, sickle cell anemia, Crohn's disease, rheumatoid arthritis, Sjögren's syndrome) or immunocompromised status due to cancer chemotherapy, hematopoietic stem cell or solid organ transplant, head and neck radiotherapy, splenectomy, chronic steroid usage * Recent history of chronic alcohol consumption of more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer, or five 5 ounce servings of wine per day * Tobacco use (former tobacco users may be enrolled, provided they have been tobacco-free for one year or more) * Diabetes mellitus * Subjects with urinalysis results suggestive of infection (if a subject meets this criterion, he/she may be rescreened for study participation when he/she no longer meets this exclusion criterion) * Medical conditions that the investigator considers significant and that may interfere with the examination or the safety of the subject * Chronic use (2 weeks or more) of medication known to affect periodontal status within one month of enrollment (such as ≥81mg aspirin, phenytoin, calcium antagonists such as nifedipine, NSAIDs, coumarin, cyclosporine, ≥10 mg/day atorvastatin or equivalent dose of another statin \[Subramanian et al, 2013\]); * Treatment with antibiotics within one month prior to enrollment * Medical condition for which antibiotic treatment during the study period is likely or a condition for which antibiotic prophylaxis is recommended before dental procedures (American Heart Association guidelines of 2007 will be followed) * Known hypersensitivity to any component of the test or placebo products * Anything that, in the opinion of the investigator, would place the subject at increased risk or prevent the subject from fully complying with or completing the study -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | up to 90 days | Adverse events will be recorded throughout the study, and may include events reported by subjects or changes observed in oral cavity examinations or vital signs (assessed at baseline, Days 3, 7, 14, 21 and 28). Blood and urine will be collected for safety labs at Days 14 and 28 after product administration, and subjects will undergo close monitoring for mucosal inflammation and irritancy and development of periodontitis, using standard clinical periodontal measurements. Follow-up will also occur at 90 days to assess for adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean MGI (Baseline and 28 Days) | 28 days | MGI is a visual index used to score gingival inflammation on a scale of 0-4. Higher scores indicate increasing levels of gingival inflammation (worse outcome). |
| Change in Percent Bleeding on Probing (Baseline and 28 Days) | 28 days | Gingival Bleeding was assessed using the dichotomous bleeding on probing index Bleeding on probing is reported as the percentage of tooth-sites that bleed on probing within a subject and higher BOP values indicate greater gingival inflammation. |
| Change in PI (Baseline and 28 Days) | 28 days | Plaque index (PI) is a visual index used to score (ranging from 0 to 5). A higher score is indicative of higher plaque build-up (worse outcome). |
Countries
United States
Participant flow
Pre-assignment details
Per protocol, 125 subjects were planned to be included in the efficacy population who had a baseline and at least 1 post-baseline assessment of 1 or more of the secondary efficacy outcome measures. Per protocol, subjects who dropped out or withdrew prior to Day 14 were replaced in the efficacy population. Two subjects were dropped out before Day 14, thus were replaced.
Participants by arm
| Arm | Count |
|---|---|
| BLXA4-ME Oral Rinse Group The treatment group received daily BLXA4-ME 1μM concentration in an oral rinse | 50 |
| Placebo Rinse Group The study group received placebo rinse similar to the rinse used by the treatment group except BLXA4-ME. | 50 |
| No-rinse Control Group The study group was a control group with no-rinse. | 27 |
| Total | 127 |
Baseline characteristics
| Characteristic | BLXA4-ME Oral Rinse Group | Total | No-rinse Control Group | Placebo Rinse Group |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 127 Participants | 27 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 24 Participants | 0 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 99 Participants | 27 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 0 Participants | 2 Participants |
| Modified Gingival Index | 2.25 units on a scale STANDARD_DEVIATION 0.141 | 2.26 units on a scale STANDARD_DEVIATION 0.171 | 2.22 units on a scale STANDARD_DEVIATION 0.174 | 2.30 units on a scale STANDARD_DEVIATION 0.19 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 9 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 28 Participants | 7 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 26 Participants | 80 Participants | 17 Participants | 37 Participants |
| Region of Enrollment United States | 50 participants | 127 participants | 27 participants | 50 participants |
| Sex: Female, Male Female | 22 Participants | 73 Participants | 16 Participants | 35 Participants |
| Sex: Female, Male Male | 28 Participants | 54 Participants | 11 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 | 0 / 27 |
| other Total, other adverse events | 18 / 50 | 10 / 50 | 3 / 27 |
| serious Total, serious adverse events | 1 / 50 | 0 / 50 | 0 / 27 |
Outcome results
Primary
Incidence of Adverse Events
Adverse events will be recorded throughout the study, and may include events reported by subjects or changes observed in oral cavity examinations or vital signs (assessed at baseline, Days 3, 7, 14, 21 and 28). Blood and urine will be collected for safety labs at Days 14 and 28 after product administration, and subjects will undergo close monitoring for mucosal inflammation and irritancy and development of periodontitis, using standard clinical periodontal measurements. Follow-up will also occur at 90 days to assess for adverse events.
Time frame: up to 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BLXA4-ME Oral Rinse | Incidence of Adverse Events | 19 Participants |
| Placebo Oral Rinse | Incidence of Adverse Events | 10 Participants |
| No Rinse Control | Incidence of Adverse Events | 3 Participants |
Secondary
Change in Mean MGI (Baseline and 28 Days)
MGI is a visual index used to score gingival inflammation on a scale of 0-4. Higher scores indicate increasing levels of gingival inflammation (worse outcome).
Time frame: 28 days
Population: The efficacy population consisted of all subjects from the safety population who had a baseline and at least 1 post-baseline assessment of 1 or more of the secondary efficacy outcome measures. Subjects who dropped out or withdrew prior to Day 14 were replaced in the efficacy population. For the efficacy evaluations, subjects were analyzed according to the treatment actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BLXA4-ME Oral Rinse | Change in Mean MGI (Baseline and 28 Days) | -0.27 units on a scale | Standard Error 0.029 |
| Placebo Oral Rinse | Change in Mean MGI (Baseline and 28 Days) | -0.21 units on a scale | Standard Error 0.029 |
| No Rinse Control | Change in Mean MGI (Baseline and 28 Days) | -0.17 units on a scale | Standard Error 0.038 |
Secondary
Change in Percent Bleeding on Probing (Baseline and 28 Days)
Gingival Bleeding was assessed using the dichotomous bleeding on probing index Bleeding on probing is reported as the percentage of tooth-sites that bleed on probing within a subject and higher BOP values indicate greater gingival inflammation.
Time frame: 28 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BLXA4-ME Oral Rinse | Change in Percent Bleeding on Probing (Baseline and 28 Days) | -12.67 percentage of tooth sites | Standard Error 1.59 |
| Placebo Oral Rinse | Change in Percent Bleeding on Probing (Baseline and 28 Days) | -12.32 percentage of tooth sites | Standard Error 1.588 |
| No Rinse Control | Change in Percent Bleeding on Probing (Baseline and 28 Days) | -9.53 percentage of tooth sites | Standard Error 2.14 |
Secondary
Change in PI (Baseline and 28 Days)
Plaque index (PI) is a visual index used to score (ranging from 0 to 5). A higher score is indicative of higher plaque build-up (worse outcome).
Time frame: 28 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| BLXA4-ME Oral Rinse | Change in PI (Baseline and 28 Days) | -0.08 units on a scale | Standard Error 0.044 |
| Placebo Oral Rinse | Change in PI (Baseline and 28 Days) | -0.12 units on a scale | Standard Error 0.044 |
| No Rinse Control | Change in PI (Baseline and 28 Days) | -0.00 units on a scale | Standard Error 0.06 |