Doxepin Hydrochloride in Treating Oral Mucositis Pain in... | NCT01156142

ID	Type	Description	Link
NCI-2011-02049	Registry Identifier	CTRP (Clinical Trials Reporting System)
CDR0000675520	Registry Identifier	PDQ (Physician Data Query)
U10CA037404	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm I	Experimental	Patients receive doxepin hydrochloride oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.	Drug: doxepin hydrochloride
Arm II	Placebo Comparator	Patients receive placebo oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2.	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
doxepin hydrochloride	Drug	Oral rinse	Arm I
placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Total Pain Reduction (Mouth and Throat)	The total pain reduction will be calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes your MOUTH PAIN due to your radiation treatment now?') used 11-point numerical analog scales (0 (no pain) to 10 (worst pain imaginable or possible) scores) to measure pain. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.	Baseline and Day 1

Secondary Outcomes

Measure	Description	Time Frame
Total Taste of the Oral Rinse	The total taste of the oral rinse will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6 , and analyzed in the same way as the primary endpoint. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes the TASTE OF THE ORAL RINSE now?') used 11-point numerical analog scales (0 (acceptable taste) to 10(terrible taste), with higher values representing worse outcome) to evaluate the total taste of the oral rinse. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.

Eligibility Module

Name	Affiliation	Role
Robert C. Miller, MD	Mayo Clinic	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Scottsdale		Scottsdale	Arizona	85259-5499	United States
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
24733799	Derived	Leenstra JL, Miller RC, Qin R, Martenson JA, Dornfeld KJ, Bearden JD, Puri DR, Stella PJ, Mazurczak MA, Klish MD, Novotny PJ, Foote RL, Loprinzi CL. Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). J Clin Oncol. 2014 May 20;32(15):1571-7. doi: 10.1200/JCO.2013.53.2630. Epub 2014 Apr 14.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
BG001	Arm II (Placebo-Doxepin)	Patients receive 2.5 mL placebo (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00062(39.0 to 93.0) BG00160(37.0 to 86.0) BG00261(37.0 to 93.0)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00013 BG00115 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00069 BG00171 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Total Pain Reduction (Mouth and Throat)

The total pain reduction will be calculated by the (average of mouth and throat) area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes your MOUTH PAIN due to your radiation treatment now?') used 11-point numerical analog scales (0 (no pain) to 10 (worst pain imaginable or possible) scores) to measure pain. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.

If a patient cancels, is missing baseline data, or only provides baseline data, he/she will be excluded from the statistical analysis. The primary analysis of the total pain reduction will only use primary data from the first phase.

Posted

Mean

Standard Deviation

units on a scale

Baseline and Day 1

ID	Title	Description
OG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
OG001	Arm II (Placebo-Doxepin)	Patients receive 2.5 mL placebo (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2.

Units	Counts
Participants	OG00069 OG00171

Title

Denominators

Categories

Title	Measurements
	OG000-9.1± 7.9 OG001-4.7± 6.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Wilcoxon (Mann-Whitney)		<0.001		Mean Difference (Final Values)	-4.4			2-Sided	95	-6.7	-2.1					Superiority or Other

Secondary

Total Taste of the Oral Rinse

The total taste of the oral rinse will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6 , and analyzed in the same way as the primary endpoint. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes the TASTE OF THE ORAL RINSE now?') used 11-point numerical analog scales (0 (acceptable taste) to 10(terrible taste), with higher values representing worse outcome) to evaluate the total taste of the oral rinse. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.

If a patient cancels, is missing baseline data, or only provides baseline data, he/she will be excluded from the statistical analysis.

Posted

Mean

Standard Deviation

units on a scale

Up to 9 days

ID	Title	Description
OG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
OG001	Arm II (Placebo-Doxepin)

Secondary

Total Stinging or Burning From the Oral Rinse

The total stinging or burning from the oral rinse will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes any STINGING OR BURNING FROM THE ORAL RINSE now?') used 11-point numerical analog scales (0 (no stinging or burning) to 10 (worst stinging or burning possible) scores) to total stinging or burning from the oral rinse. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs.The statistical analysis will be the same as the primary analysis.

If a patient cancels, is missing baseline data, or only provides baseline data, he/she will be excluded from the statistical analysis.

Posted

Mean

Standard Deviation

units on a scale

Up to 9 days

ID	Title	Description
OG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
OG001

Secondary

Total Drowsiness Increase

The total drowsiness increase will be calculated by the area under the curve (AUC) adjusting for baseline, with time scale replaced by a numerical scale of 1,2,3,4,5,6. The numerical scale will be used rather than the raw time scale in order to give proper weights to more immediate patient-reported mouth pain outcomes after treatment. The AUC will be calculated by proration when there are terminal missing data. If the missing data are intermittent, simple imputation will be applied to calculate the AUC. The question ('On a scale from 0 to 10, what number best describes your DROWSINESS now?') used 11-point numerical analog scales (0 (no drowsiness) to 10 (extreme drowsiness, leading to sleep) scores) to measure total drowsiness increase. The AUCs for the two treatment arms were compared by using the Wilcoxon rank sum test with 95% CIs. The statistical analysis will be the same as the primary analysis.

If a patient cancels, is missing baseline data, or only provides baseline data, he/she will be excluded from the statistical analysis.

Posted

Mean

Standard Deviation

units on a scale

Up to 9 days

ID	Title	Description
OG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
OG001	Arm II (Placebo-Doxepin)

Secondary

Incidence of Using Alternative Analgesics Between 2 and 4 Hours After the Initial Mouthwash

The incidence of utilizing additional analgesics between 2 and 4 hours after the initial mouthwash will be compared between the arms by the Chi-square test .

Posted

Number

percentage of patients

Up to 9 days

ID	Title	Description
OG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
OG001	Arm II (Placebo-Doxepin)	Patients receive 2.5 mL placebo (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2.

Units	Counts
Participants	OG000

Secondary

Patient Preference for Continuing Therapy With Oral Doxepin Hydrochloride

After each dose was administered, patients were asked if they would like to continue rinses with that particular agent. The percentage of patients who expressed an interest in continuing therapy are reported below.

Posted

Number

percentage of patients

Up to 9 days

ID	Title	Description
OG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.
OG001	Arm II (Placebo-Doxepin)	Patients receive 2.5 mL placebo (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm I (Doxepin-Placebo)	Patients receive (10 mg/mL x 2.5 mL) 25 mg doxepin hydrochloride (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm II on day 2.			0	74	10	74
EG001	Arm II (Placebo-Doxepin)	Patients receive 2.5 mL placebo (diluted to 5 mL with 2.5 mL of sterile water for irrigation, or sterile water for injection, or distilled water) oral rinse (swish, gargle, and spit) over 1 minute on day 1. Patients may crossover to arm I on day 2.			0	75	8	75

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0010 events0 affected75 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0004 events3 affected74 at risk EG0010 events0 affected75 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0010 events0 affected75 at risk
Mucositis oral	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0009 events4 affected74 at risk EG00112 events6 affected75 at risk
Nausea	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0012 events1 affected75 at risk
Oral pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0005 events2 affected74 at risk EG0012 events2 affected75 at risk
Salivary duct inflammation	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0010 events0 affected75 at risk
Vomiting	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected74 at risk EG0012 events1 affected75 at risk
Fatigue	General disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0010 events0 affected75 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0010 events0 affected75 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected74 at risk EG0012 events1 affected75 at risk
Lethargy	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected74 at risk EG0011 events1 affected75 at risk
Somnolence	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0012 events2 affected75 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected74 at risk EG0010 events0 affected75 at risk

Ancestor Terms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D005759	Gastroenteritis
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D009059	Mouth Diseases
D009057	Stomatognathic Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009447	Neuroblastoma
D018241	Neuroectodermal Tumors, Primitive, Peripheral
D018242	Neuroectodermal Tumors, Primitive
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009380	Neoplasms, Nerve Tissue
D020431	Olfactory Nerve Diseases
D003389	Cranial Nerve Diseases
D009422	Nervous System Diseases
D009062	Mouth Neoplasms
D012466	Salivary Gland Diseases
D014060	Tongue Diseases

ID	Term
D006258	Head and Neck Neoplasms
D052016	Mucositis
D010146	Pain
D000077195	Squamous Cell Carcinoma of Head and Neck
D018304	Esthesioneuroblastoma, Olfactory
D012468	Salivary Gland Neoplasms
D014062	Tongue Neoplasms

ID	Term
D010082	Oxepins
D004988	Ethers, Cyclic
D004987	Ethers
D009930	Organic Chemicals
D003990	Dibenzoxepins
D006575	Heterocyclic Compounds, 3-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds