Trial Outcomes & Findings for Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy (NCT NCT02229539)

Last Updated: 2025-05-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

275 participants

Primary outcome timeframe

Baseline, 5, 15, 30, 60, 120, 240 minutes post treatment

Results posted on

2025-05-18

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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).	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).	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).
Cycle 1 (Treatment Per Protocol) STARTED	78	76	76
Cycle 1 (Treatment Per Protocol) COMPLETED	78	75	74
Cycle 1 (Treatment Per Protocol) NOT COMPLETED	0	1	2
Cycle 2 (Optional Continuation Phase) STARTED	35	38	32
Cycle 2 (Optional Continuation Phase) COMPLETED	28	31	22
Cycle 2 (Optional Continuation Phase) NOT COMPLETED	7	7	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).	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).
Cycle 1 (Treatment Per Protocol) Withdrawal by Subject	0	1	0
Cycle 1 (Treatment Per Protocol) Alternate Therapy	0	0	1
Cycle 1 (Treatment Per Protocol) Medical Problems	0	0	1
Cycle 2 (Optional Continuation Phase) Withdrawal by Subject	5	6	8
Cycle 2 (Optional Continuation Phase) Adverse Event	2	0	0
Cycle 2 (Optional Continuation Phase) Alternative Therapy	0	1	2

Baseline Characteristics

Doxepin and a Topical Rinse in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Radiotherapy With or Without Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doxepin n=78 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=76 Participants 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).	Placebo n=76 Participants 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).	Total n=230 Participants Total of all reporting groups
Age, Continuous	61.5 years n=93 Participants	60.0 years n=4 Participants	60.0 years n=27 Participants	60 years n=483 Participants
Age, Customized <60 years old	35 Participants n=93 Participants	34 Participants n=4 Participants	37 Participants n=27 Participants	106 Participants n=483 Participants
Age, Customized >=60 years old	43 Participants n=93 Participants	42 Participants n=4 Participants	39 Participants n=27 Participants	124 Participants n=483 Participants
Sex: Female, Male Female	19 Participants n=93 Participants	18 Participants n=4 Participants	19 Participants n=27 Participants	56 Participants n=483 Participants
Sex: Female, Male Male	59 Participants n=93 Participants	58 Participants n=4 Participants	57 Participants n=27 Participants	174 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	7 Participants n=4 Participants	4 Participants n=27 Participants	13 Participants n=483 Participants
Race (NIH/OMB) White	75 Participants n=93 Participants	67 Participants n=4 Participants	71 Participants n=27 Participants	213 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Region of Enrollment United States	78 participants n=93 Participants	76 participants n=4 Participants	76 participants n=27 Participants	230 participants n=483 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0=Asymptomatic and fully active	37 Participants n=93 Participants	31 Participants n=4 Participants	33 Participants n=27 Participants	101 Participants n=483 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1=Symptomatic and fully ambulatory	40 Participants n=93 Participants	39 Participants n=4 Participants	40 Participants n=27 Participants	119 Participants n=483 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2=Symptomatic, <50% in bed during the day	1 Participants n=93 Participants	6 Participants n=4 Participants	3 Participants n=27 Participants	10 Participants n=483 Participants
Concurrent use of chemotherapy Yes	62 Participants n=93 Participants	62 Participants n=4 Participants	64 Participants n=27 Participants	188 Participants n=483 Participants
Concurrent use of chemotherapy No	16 Participants n=93 Participants	14 Participants n=4 Participants	12 Participants n=27 Participants	42 Participants n=483 Participants
Mucous Membrane Grade 1	17 Participants n=93 Participants	16 Participants n=4 Participants	16 Participants n=27 Participants	49 Participants n=483 Participants
Mucous Membrane Grade 2	47 Participants n=93 Participants	48 Participants n=4 Participants	49 Participants n=27 Participants	144 Participants n=483 Participants
Mucous Membrane Grade 3 or more	14 Participants n=93 Participants	12 Participants n=4 Participants	11 Participants n=27 Participants	37 Participants n=483 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Doxepin n=78 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=76 Participants 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).	Placebo n=76 Participants 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).
Mean Area Under the Curve (AUC) of Total Pain Reduction	11.6 units on a scale*time scale Standard Deviation 9.7	11.7 units on a scale*time scale Standard Deviation 8.1	8.7 units on a scale*time scale Standard Deviation 9.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Doxepin n=78 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=76 Participants 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).	Placebo n=76 Participants 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).
Area Under the Curve (AUC) of Total Unpleasant Taste of the Oral Rinse	3.5 units on a scale*units on a scale Interval 0.0 to 8.5	2.0 units on a scale*units on a scale Interval 0.0 to 6.3	0.8 units on a scale*units on a scale Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Doxepin n=78 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=76 Participants 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).	Placebo n=76 Participants 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).
Area Under the Curve (AUC) of Total Stinging or Burning From the Oral Rinse	5.3 units on a scale*units on a scale Interval 2.5 to 11.0	0.8 units on a scale*units on a scale Interval 0.0 to 4.8	0.5 units on a scale*units on a scale Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Doxepin n=78 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=76 Participants 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).	Placebo n=76 Participants 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).
Area Under the Curve (AUC) of Total Drowsiness	0 units on a scale*units on a scale Interval -2.5 to 3.0	-1.8 units on a scale*units on a scale Interval -7.3 to 0.0	0 units on a scale*units on a scale Interval -8.0 to 0.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Doxepin n=78 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=76 Participants 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).	Placebo n=76 Participants 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).
The Incidence of Using Alternative Analgesics 120 minutes	10 Participants	7 Participants	14 Participants
The Incidence of Using Alternative Analgesics 240 minutes	13 Participants	14 Participants	21 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Doxepin n=75 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=73 Participants 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).	Placebo n=71 Participants 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).
Patient Preference for Continued Therapy With Oral Rinse After Initial Test Rinse Phase	45 Participants	46 Participants	38 Participants

SECONDARY outcome

Timeframe: 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.

Patients were asked: "Did you use the study rinse today?" daily questionnaire during the optional continuation phase (Cycle 2).

Outcome measures

Outcome measures
Measure	Doxepin n=35 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=38 Participants 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).	Placebo n=32 Participants 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).
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 1 · Yes	33 Participants	37 Participants	30 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 1 · No	2 Participants	0 Participants	1 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 2 · Yes	30 Participants	33 Participants	25 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 2 · No	4 Participants	3 Participants	3 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 3 · Yes	30 Participants	27 Participants	22 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 3 · No	4 Participants	8 Participants	5 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 4 · Yes	29 Participants	25 Participants	18 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 4 · No	3 Participants	8 Participants	7 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 5 · Yes	27 Participants	24 Participants	17 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 5 · No	5 Participants	6 Participants	7 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 6 · Yes	27 Participants	26 Participants	14 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 6 · No	5 Participants	4 Participants	7 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 7 · Yes	24 Participants	25 Participants	15 Participants
Frequency of Study Rinse Used in the Continuation Phase Cycle 2 Day 7 · No	6 Participants	6 Participants	7 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Doxepin n=35 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=38 Participants 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).	Placebo n=32 Participants 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).
Median Mouth Pain Score in the Continuation Phase Cycle 2 Day 1	6.0 units on a scale Interval 0.0 to 9.0	5.5 units on a scale Interval 1.0 to 9.0	5.0 units on a scale Interval 1.0 to 9.0
Median Mouth Pain Score in the Continuation Phase Cycle 2 Day 2	5.0 units on a scale Interval 0.0 to 9.0	5.5 units on a scale Interval 1.0 to 8.0	5.0 units on a scale Interval 1.0 to 9.0
Median Mouth Pain Score in the Continuation Phase Cycle 2 Day 3	5.0 units on a scale Interval 0.0 to 10.0	5.0 units on a scale Interval 1.0 to 8.0	5.0 units on a scale Interval 1.0 to 9.0
Median Mouth Pain Score in the Continuation Phase Cycle 2 Day 4	5.0 units on a scale Interval 0.0 to 9.0	5.0 units on a scale Interval 1.0 to 9.0	5.0 units on a scale Interval 2.0 to 9.0
Median Mouth Pain Score in the Continuation Phase Cycle 2 Day 5	5.0 units on a scale Interval 0.0 to 9.0	5.0 units on a scale Interval 1.0 to 8.0	5.0 units on a scale Interval 0.0 to 9.0
Median Mouth Pain Score in the Continuation Phase Cycle 2 Day 6	5.5 units on a scale Interval 0.0 to 9.0	5.0 units on a scale Interval 1.0 to 9.0	4.0 units on a scale Interval 2.0 to 9.0
Median Mouth Pain Score in the Continuation Phase Cycle 2 Day 7	5.0 units on a scale Interval 0.0 to 9.0	5.0 units on a scale Interval 1.0 to 8.0	4.5 units on a scale Interval 2.0 to 10.0

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Doxepin n=35 Participants 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=38 Participants 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).	Placebo n=32 Participants 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).
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 1 · Yes	22 Participants	20 Participants	21 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 1 · No	12 Participants	15 Participants	10 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 2 · Yes	19 Participants	22 Participants	19 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 2 · No	14 Participants	14 Participants	8 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 3 · Yes	17 Participants	19 Participants	17 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 3 · No	16 Participants	15 Participants	7 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 4 · Yes	20 Participants	22 Participants	16 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 4 · No	11 Participants	10 Participants	7 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 5 · Yes	19 Participants	16 Participants	15 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 5 · No	10 Participants	14 Participants	7 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 6 · Yes	22 Participants	20 Participants	14 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 6 · No	8 Participants	11 Participants	7 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 7 · Yes	17 Participants	19 Participants	13 Participants
The Incidence of Using Alternative Analgesics in the Continuation Phase Cycle 2 Day 7 · No	8 Participants	11 Participants	6 Participants

Adverse Events

Doxepin

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

DLA (Diphenhydramine, Lidocaine and Antacid)

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Doxepin n=78 participants at risk 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).	Placebo n=72 participants at risk 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).	DLA (Diphenhydramine, Lidocaine and Antacid) n=74 participants at risk 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).
Cardiac disorders Sinus tachycardia	1.3% 1/78 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/72 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/74 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Gastrointestinal disorders Constipation	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/72 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/74 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Gastrointestinal disorders Dry mouth	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/72 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/74 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Gastrointestinal disorders Dysphagia	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/72 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	2.7% 2/74 • Number of events 2 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Gastrointestinal disorders Oral pain	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/72 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/74 • Number of events 2 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
General disorders Fatigue	1.3% 1/78 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/72 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/74 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
General disorders Fever	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/72 • Number of events 2 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/74 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
General disorders Malaise	1.3% 1/78 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/72 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/74 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Infections and infestations Stoma site infection	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/72 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/74 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Infections and infestations Urinary tract infection	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/72 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/74 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Metabolism and nutrition disorders Dehydration	1.3% 1/78 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/72 • Number of events 1 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/74 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).
Vascular disorders Thromboembolic event	0.00% 0/78 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	0.00% 0/72 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).	1.4% 1/74 • Number of events 2 • In clinic at 5, 15, 30, and 60 minutes after oral rinse and daily for up to 7 days, beginning within 1 week of Day 1. 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, started the treatment and had adverse events assessed during the reporting period. Adverse events were not assessed on six participants (2 DLA and 4 Placebo).

Other adverse events

Additional Information

Robert C. Miller, MD, MS

Mayo Clinic

Phone: 904-953-1003

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60