Acute Oral Mucositis Pain
Conditions
Brief summary
The purpose of this study is to test whether a mouthwash made with a drug called doxepin can reduce the pain caused by mouth sores resulting from radiation therapy. A number of mouth rinse preparations exist for patients with treatment-related oral mucositis pain such as the DLA rinse, an over-the-counter medication. This study will evaluate the effects of doxepin compared to DLA (diphenhydramine, lidocaine and antacids) and placebo.Doxepin is approved by the Food and Drug Administration (FDA) for the treatment of depression, anxiety, long-term pain management, as well as management of rash.
Detailed description
Patients are stratified according to sex (male vs. female), concurrent use of chemotherapy (no vs. yes), patient age at registration (\< 60 years old vs. ≥ 60 years old and RTOG acute radiation morbidity criteria (1 vs. 2 vs 3 or more). Protocol therapy will consist of 2 cycles. Patients are randomized to one of three treatment regimens, which include doxepin, DLA and placebo. Cycle One will consist of one day. The care provider or nurse will confirm that the oral pain is at least 4 out of 10 severity level at the time of the rinse on the first day of the study. Patient will be asked to complete the baseline evaluation in the Oral Symptoms booklet. If the pain score is less than 4 then administration will be delayed until the pain is at least 4. Cycle Two will consist of an optional continuation phase lasting up to 7 days. Initiation of the Cycle 2/Continuation Phase may be delayed up to one week after Cycle 1/Day 1. Primary Objective: 1\. Determine whether the doxepin rinse or DLA rinse is more effective than placebo in reducing OM-related pain in patients undergoing RT to the oral cavity, as measured by a patient-reported questionnaire at baseline, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours. Secondary Objectives: 1. Assess the adverse event profile of the doxepin rinse, the DLA rinse agent, and the placebo using a patient-reported questionnaire at 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours for domains of unpleasant taste, burning or stinging discomfort, and drowsiness. 2. Compare the incidence of using additional analgesics between 1 and 4 hours after the initial mouthwash, between the doxepin oral rinse, the DLA rinse agent, and the placebo arms. 3. Compare the length of time that each study product is used by patients in the one-week continuation phase. 4. Compare the daily pain scores in the one-week continuation phase for the three study arms. 5. Compare the 24-hour morphine equivalent dose used in the continuation phase for the three study arms.
Interventions
DRUGdoxepin hydrochloride oral solution
2.5 mL (25 mg) doxepin and 2.5 mL water administered orally
DRUGDLA (diphenhydramine, lidocaine and antacids) rinse
5.0 mL administered orally
OTHERPlacebo
2.5 mL placebo and 2.5 mL water administered orally
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documentation of Disease: Histologic documentation of malignancy currently undergoing a course of RT (with or without chemotherapy) including the oral cavity and/or oropharyngeal area to a dose of at least 4500 cGy using more than 5 fractions (i.e., stereotactic body radiation therapy \[SBRT\] is not allowed). 2. Physical exam demonstrating evidence of radiotherapy-related mucositis in the visible oral cavity and/or oropharynx consistent with mucous membrane toxicity greater than 0 using the Acute Radiation Morbidity Scoring Criteria. 3. At least 4 (out of 10) patient-reported oral pain related to oral mucositis secondary to RT for which the patient seeks relief, as measured on the Oral Pain Assessment. Note: The pain score must be at least 4 at the time that the patient starts the first dose of study medication. The patient may be enrolled to the study if s/he, at times, has a pain score of at least 4, so long as initiation of study treatment begins when the pain score is at least 4. 4. Ability to complete questionnaire(s) by themselves or with assistance. 5. No known allergy to diphenhydramine, lidocaine, antacid (aluminum hydroxide, magnesium hydroxide, and simethicone), doxepin, tricyclic antidepressants, or any known component of the drug formulation in the testing arms. 6. No use of any anti-arrhythmic medication (except for beta-blockers) including lidocaine, linezolid, ipratropium, or medications with high anti-cholinergic potency (including neostigmine, a tricyclic antidepressant or a monoamine oxidase inhibitor) within 2 weeks prior to registration. 7. No current diagnosed untreated or unresolved oral candidiasis or oral HSV infection. 8. No history of untreated narrow angle glaucoma within 6 weeks prior to registration. 9. No untreated urinary retention within 6 weeks prior to registration. 10. No current use of glutamine or sucralfate powders at the time of registration (no washout required). 11. No cryotherapy for prophylactic mucosal protection within 6 weeks prior to registration. 12. Not pregnant, because patients eligible for this study will be receiving radiotherapy, which has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 28 days prior to registration is required. 13. Age ≥ 18 years 14. ECOG Performance Status 0, 1, or 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Curve (AUC) of Total Pain Reduction | Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment | Total pain reduction (mouth and throat) was measured by the numerical analogue scale of mouth pain on a scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total pain reduction was calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse | 5, 15, 30, 60, 120, 240 minutes post treatment | Total stinging or burning was measured by the numerical analogue scale of stinging or burning from the oral rinse on a scale of 0 to 10, with 0=no stinging or burning and 10=worst stinging or burning possible in the questionnaires taken at 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total stinging or burning was calculated by the area under the curve (AUC) adjusting for 5 minutes post treatment, with time scale (5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 1, 2, 3, 4 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing 5 minutes after treatment data, or only provided 5 minutes after treatment data, he/she was excluded from the statistical analysis. |
| Area Under the Curve (AUC) of Total Drowsiness | Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment | Total drowsiness was measured by the numerical analogue scale of drowsiness on a scale of 0 to 10, with 0=no drowsiness and 10=extreme drowsiness, leading to sleep in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total drowsiness was calculated by the area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis. |
| The Incidence of Using Alternative Analgesics | At 120 and 240 minutes post treatment | Patients were asked if they have taken any other pain medications, if yes, to record the name, strength and when they have taken the pain medications in the 120 minutes and 240 minutes post treatment questionnaires. |
| Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse | 5, 15, 30, 60, 120, 240 minutes post treatment | Total unpleasant taste was measured by the numerical analogue scale of taste of the oral rinse on a scale of 0 to 10, with 0=acceptable and 10=terrible in the questionnaires taken at 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total unpleasant taste was calculated by the area under the curve (AUC) adjusting for 5 minutes post treatment, with time scale (5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 1, 2, 3, 4 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing 5 minutes after treatment data, or only provided 5 minutes after treatment data, he/she was excluded from the statistical analysis. |
| Frequency of Study Rinse Used in the Continuation Phase | Up to 7 days. | Patients were asked: Did you use the study rinse today? daily questionnaire during the optional continuation phase (Cycle 2). |
| Median Mouth Pain Score in the Continuation Phase | Day 1 to Day 7 in the Continuation Phase | Mouth pain scores was measured using the numerical analogue scale ranging from scale of 0 to 10, with 0=no pain and 10=worst pain daily during the optional continuation phase (Cycle 2). |
| The Incidence of Using Alternative Analgesics in the Continuation Phase | Day 1 to Day 7 in the Continuation Phase | Patients were asked if they have taken any medications for pain over the past 24 hours, if yes, to record the name, strength and when they have taken the pain medications daily during the optional continuation phase (Cycle 2). |
| Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase | At 240 minutes post treatment | Patients were asked: Based on your experience with this current oral rinsing medication, would you want to take another dose now if it were available? in the 240 minutes post treatment questionnaire. |
Countries
United States
Participant flow
Recruitment details
Two-hundred and seventy-five participants (92 Doxepin, 91 DLA and 92 Placebo) were enrolled between November 2014 to May 2016. Data as of 8/21/2017 was summarized and reported.
Pre-assignment details
Total of 45 participants were excluded from all analyses due to 23 cancellations, 19 with mouth pain score\<4 prior to treatment, 1 ineligible, 1 did not return questionnaire booklet and 1 inadvertently unblinding by study team.
Participants by arm
| Arm | Count |
|---|---|
| Doxepin Patients receive 2.5 mL (25 mg) doxepin and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2). | 78 |
| DLA (Diphenhydramine, Lidocaine and Antacid) Patients receive 5.0 mL DLA orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2). | 76 |
| Placebo Patients receive 2.5 mL placebo and 2.5 mL water orally in the clinic on Day 1 (Cycle 1). Patients will be encouraged to continue treatment with the study agent for an additional week (Cycle 2). | 76 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Cycle 1 (Treatment Per Protocol) | Alternate Therapy | 0 | 0 | 1 |
| Cycle 1 (Treatment Per Protocol) | Medical Problems | 0 | 0 | 1 |
| Cycle 1 (Treatment Per Protocol) | Withdrawal by Subject | 0 | 1 | 0 |
| Cycle 2 (Optional Continuation Phase) | Adverse Event | 2 | 0 | 0 |
| Cycle 2 (Optional Continuation Phase) | Alternative Therapy | 0 | 1 | 2 |
| Cycle 2 (Optional Continuation Phase) | Withdrawal by Subject | 5 | 6 | 8 |
Baseline characteristics
| Characteristic | Doxepin | DLA (Diphenhydramine, Lidocaine and Antacid) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 61.5 years | 60.0 years | 60.0 years | 60 years |
| Age, Customized <60 years old | 35 Participants | 34 Participants | 37 Participants | 106 Participants |
| Age, Customized >=60 years old | 43 Participants | 42 Participants | 39 Participants | 124 Participants |
| Concurrent use of chemotherapy No | 16 Participants | 14 Participants | 12 Participants | 42 Participants |
| Concurrent use of chemotherapy Yes | 62 Participants | 62 Participants | 64 Participants | 188 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0=Asymptomatic and fully active | 37 Participants | 31 Participants | 33 Participants | 101 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1=Symptomatic and fully ambulatory | 40 Participants | 39 Participants | 40 Participants | 119 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2=Symptomatic, <50% in bed during the day | 1 Participants | 6 Participants | 3 Participants | 10 Participants |
| Mucous Membrane Grade 1 | 17 Participants | 16 Participants | 16 Participants | 49 Participants |
| Mucous Membrane Grade 2 | 47 Participants | 48 Participants | 49 Participants | 144 Participants |
| Mucous Membrane Grade 3 or more | 14 Participants | 12 Participants | 11 Participants | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 75 Participants | 67 Participants | 71 Participants | 213 Participants |
| Region of Enrollment United States | 78 participants | 76 participants | 76 participants | 230 participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 19 Participants | 56 Participants |
| Sex: Female, Male Male | 59 Participants | 58 Participants | 57 Participants | 174 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 78 | 0 / 76 | 0 / 76 |
| other Total, other adverse events | 17 / 78 | 7 / 72 | 8 / 74 |
| serious Total, serious adverse events | 2 / 78 | 3 / 72 | 3 / 74 |
Outcome results
Primary
Mean Area Under the Curve (AUC) of Total Pain Reduction
Total pain reduction (mouth and throat) was measured by the numerical analogue scale of mouth pain on a scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total pain reduction was calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis.
Time frame: Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment
Population: All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain and started the treatment and had mouth and throat pain data at baseline and at least one time point beyond baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxepin | Mean Area Under the Curve (AUC) of Total Pain Reduction | 11.6 units on a scale*time scale | Standard Deviation 9.7 |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Mean Area Under the Curve (AUC) of Total Pain Reduction | 11.7 units on a scale*time scale | Standard Deviation 8.1 |
| Placebo | Mean Area Under the Curve (AUC) of Total Pain Reduction | 8.7 units on a scale*time scale | Standard Deviation 9.9 |
p-value: 0.02Wilcoxon rank-sum
p-value: 0.004Wilcoxon rank-sum
Secondary
Area Under the Curve (AUC) of Total Drowsiness
Total drowsiness was measured by the numerical analogue scale of drowsiness on a scale of 0 to 10, with 0=no drowsiness and 10=extreme drowsiness, leading to sleep in the questionnaires taken at baseline, and 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total drowsiness was calculated by the area under the curve (AUC) adjusting for baseline, with time scale (baseline, 5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 0, 1, 2, 3, 4, 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing baseline data, or only provided baseline data, he/she was excluded from the statistical analysis.
Time frame: Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxepin | Area Under the Curve (AUC) of Total Drowsiness | 0 units on a scale*units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Area Under the Curve (AUC) of Total Drowsiness | -1.8 units on a scale*units on a scale |
| Placebo | Area Under the Curve (AUC) of Total Drowsiness | 0 units on a scale*units on a scale |
Secondary
Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse
Total stinging or burning was measured by the numerical analogue scale of stinging or burning from the oral rinse on a scale of 0 to 10, with 0=no stinging or burning and 10=worst stinging or burning possible in the questionnaires taken at 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total stinging or burning was calculated by the area under the curve (AUC) adjusting for 5 minutes post treatment, with time scale (5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 1, 2, 3, 4 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing 5 minutes after treatment data, or only provided 5 minutes after treatment data, he/she was excluded from the statistical analysis.
Time frame: 5, 15, 30, 60, 120, 240 minutes post treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxepin | Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse | 5.3 units on a scale*units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse | 0.8 units on a scale*units on a scale |
| Placebo | Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse | 0.5 units on a scale*units on a scale |
Secondary
Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse
Total unpleasant taste was measured by the numerical analogue scale of taste of the oral rinse on a scale of 0 to 10, with 0=acceptable and 10=terrible in the questionnaires taken at 5, 15, 30, 60, 120, 240 minutes after assigned treatment for doxepin or DLA vs. placebo. The total unpleasant taste was calculated by the area under the curve (AUC) adjusting for 5 minutes post treatment, with time scale (5, 15, 30, 60, 120 and 240 minutes post treatment) replaced by a numerical scale of 1, 2, 3, 4 5 and 6 respectively. The AUC was prorated when there are terminal missing data. If the missing data were intermittent, simple imputation by trapezoidal rules were applied to calculate the AUC. If a patient cancelled, was missing 5 minutes after treatment data, or only provided 5 minutes after treatment data, he/she was excluded from the statistical analysis.
Time frame: 5, 15, 30, 60, 120, 240 minutes post treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxepin | Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse | 3.5 units on a scale*units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse | 2.0 units on a scale*units on a scale |
| Placebo | Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse | 0.8 units on a scale*units on a scale |
Secondary
Frequency of Study Rinse Used in the Continuation Phase
Patients were asked: Did you use the study rinse today? daily questionnaire during the optional continuation phase (Cycle 2).
Time frame: Up to 7 days.
Population: All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain, completed the cycle 1 treatment, has started treatment in the optional continuation phase and has responded to the question.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 6 | Yes | 27 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 3 | No | 4 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 2 | Yes | 30 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 5 | No | 5 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 4 | Yes | 29 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 1 | No | 2 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 5 | Yes | 27 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 4 | No | 3 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 6 | No | 5 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 2 | No | 4 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 7 | No | 6 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 1 | Yes | 33 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 3 | Yes | 30 Participants |
| Doxepin | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 7 | Yes | 24 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 6 | Yes | 26 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 1 | Yes | 37 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 1 | No | 0 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 2 | Yes | 33 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 2 | No | 3 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 3 | Yes | 27 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 3 | No | 8 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 4 | Yes | 25 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 4 | No | 8 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 5 | Yes | 24 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 5 | No | 6 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 6 | No | 4 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 7 | Yes | 25 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 7 | No | 6 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 7 | Yes | 15 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 5 | No | 7 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 3 | Yes | 22 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 2 | No | 3 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 6 | Yes | 14 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 2 | Yes | 25 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 1 | Yes | 30 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 6 | No | 7 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 1 | No | 1 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 4 | No | 7 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 4 | Yes | 18 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 7 | No | 7 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 5 | Yes | 17 Participants |
| Placebo | Frequency of Study Rinse Used in the Continuation Phase | Cycle 2 Day 3 | No | 5 Participants |
Secondary
Median Mouth Pain Score in the Continuation Phase
Mouth pain scores was measured using the numerical analogue scale ranging from scale of 0 to 10, with 0=no pain and 10=worst pain daily during the optional continuation phase (Cycle 2).
Time frame: Day 1 to Day 7 in the Continuation Phase
Population: All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain, completed the cycle 1 treatment, has started treatment in the optional continuation phase and has responded to the question.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Doxepin | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 2 | 5.0 units on a scale |
| Doxepin | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 5 | 5.0 units on a scale |
| Doxepin | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 4 | 5.0 units on a scale |
| Doxepin | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 1 | 6.0 units on a scale |
| Doxepin | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 7 | 5.0 units on a scale |
| Doxepin | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 6 | 5.5 units on a scale |
| Doxepin | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 3 | 5.0 units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 4 | 5.0 units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 1 | 5.5 units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 2 | 5.5 units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 3 | 5.0 units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 5 | 5.0 units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 6 | 5.0 units on a scale |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 7 | 5.0 units on a scale |
| Placebo | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 5 | 5.0 units on a scale |
| Placebo | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 2 | 5.0 units on a scale |
| Placebo | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 7 | 4.5 units on a scale |
| Placebo | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 6 | 4.0 units on a scale |
| Placebo | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 4 | 5.0 units on a scale |
| Placebo | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 3 | 5.0 units on a scale |
| Placebo | Median Mouth Pain Score in the Continuation Phase | Cycle 2 Day 1 | 5.0 units on a scale |
Secondary
Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase
Patients were asked: Based on your experience with this current oral rinsing medication, would you want to take another dose now if it were available? in the 240 minutes post treatment questionnaire.
Time frame: At 240 minutes post treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Doxepin | Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase | 45 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase | 46 Participants |
| Placebo | Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase | 38 Participants |
Secondary
The Incidence of Using Alternative Analgesics
Patients were asked if they have taken any other pain medications, if yes, to record the name, strength and when they have taken the pain medications in the 120 minutes and 240 minutes post treatment questionnaires.
Time frame: At 120 and 240 minutes post treatment
Population: Some patients are missing their Additional Analgesic Use. All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain and started the treatment and has responded to the question about if they have taken any other pain medications at the indicated time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Doxepin | The Incidence of Using Alternative Analgesics | 120 minutes | 10 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics | 240 minutes | 13 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics | 120 minutes | 7 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics | 240 minutes | 14 Participants |
| Placebo | The Incidence of Using Alternative Analgesics | 120 minutes | 14 Participants |
| Placebo | The Incidence of Using Alternative Analgesics | 240 minutes | 21 Participants |
Secondary
The Incidence of Using Alternative Analgesics in the Continuation Phase
Patients were asked if they have taken any medications for pain over the past 24 hours, if yes, to record the name, strength and when they have taken the pain medications daily during the optional continuation phase (Cycle 2).
Time frame: Day 1 to Day 7 in the Continuation Phase
Population: All participants who met eligibility criteria, had mouth pain score of at least 4 on 0 to 10 scale with higher scores indicated worst pain and started the treatment and has responded to the question about if they have taken any other pain medications at the indicated time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 1 | Yes | 22 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 7 | Yes | 17 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 3 | No | 16 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 6 | No | 8 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 5 | Yes | 19 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 4 | Yes | 20 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 2 | Yes | 19 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 4 | No | 11 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 7 | No | 8 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 6 | Yes | 22 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 2 | No | 14 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 1 | No | 12 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 5 | No | 10 Participants |
| Doxepin | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 3 | Yes | 17 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 5 | Yes | 16 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 1 | Yes | 20 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 1 | No | 15 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 2 | Yes | 22 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 2 | No | 14 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 3 | Yes | 19 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 3 | No | 15 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 4 | Yes | 22 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 4 | No | 10 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 5 | No | 14 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 6 | Yes | 20 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 6 | No | 11 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 7 | Yes | 19 Participants |
| DLA (Diphenhydramine, Lidocaine and Antacid) | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 7 | No | 11 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 2 | No | 8 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 7 | No | 6 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 5 | No | 7 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 2 | Yes | 19 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 7 | Yes | 13 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 6 | Yes | 14 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 1 | No | 10 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 1 | Yes | 21 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 4 | Yes | 16 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 6 | No | 7 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 4 | No | 7 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 3 | No | 7 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 3 | Yes | 17 Participants |
| Placebo | The Incidence of Using Alternative Analgesics in the Continuation Phase | Cycle 2 Day 5 | Yes | 15 Participants |