Trial Outcomes & Findings for Doxepin Hydrochloride in Treating Oral Mucositis Pain in Patients With Head and Neck Cancer Undergoing Radiation Therapy With or Without Chemotherapy (NCT NCT01156142)

Last Updated: 2017-08-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

155 participants

Primary outcome timeframe

Baseline and Day 1

Results posted on

2017-08-09

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	77	78
Overall Study COMPLETED	69	71
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Withdrawal by Subject	8	6
Overall Study Ineligible	0	1

Baseline Characteristics

Doxepin Hydrochloride in Treating Oral Mucositis Pain in Patients With Head and Neck Cancer Undergoing Radiation Therapy With or Without Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Doxepin-Placebo) n=69 Participants 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.	Arm II (Placebo-Doxepin) n=71 Participants 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.	Total n=140 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	60 years n=7 Participants	61 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	56 Participants n=7 Participants	112 Participants n=5 Participants
Region of Enrollment United States	69 participants n=5 Participants	71 participants n=7 Participants	140 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 1

Population: 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.

Outcome measures

Outcome measures
Measure	Arm I (Doxepin-Placebo) n=69 Participants 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.	Arm II (Placebo-Doxepin) n=71 Participants 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.
Total Pain Reduction (Mouth and Throat)	-9.1 units on a scale Standard Deviation 7.9	-4.7 units on a scale Standard Deviation 6.1

SECONDARY outcome

Timeframe: Up to 9 days

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

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.

Outcome measures

Outcome measures
Measure	Arm I (Doxepin-Placebo) n=69 Participants 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.	Arm II (Placebo-Doxepin) n=71 Participants 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.
Total Taste of the Oral Rinse	7.7 units on a scale Standard Deviation 7.1	5.1 units on a scale Standard Deviation 7.7

SECONDARY outcome

Timeframe: Up to 9 days

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

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.

Outcome measures

Outcome measures
Measure	Arm I (Doxepin-Placebo) n=69 Participants 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.	Arm II (Placebo-Doxepin) n=71 Participants 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.
Total Stinging or Burning From the Oral Rinse	9.6 units on a scale Standard Deviation 8.4	4.0 units on a scale Standard Deviation 8.0

SECONDARY outcome

Timeframe: Up to 9 days

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

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.

Outcome measures

Outcome measures
Measure	Arm I (Doxepin-Placebo) n=69 Participants 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.	Arm II (Placebo-Doxepin) n=71 Participants 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.
Total Drowsiness Increase	-0.7 units on a scale Standard Deviation 10.3	-2.4 units on a scale Standard Deviation 6.6

SECONDARY outcome

Timeframe: Up to 9 days

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 .

Outcome measures

Outcome measures
Measure	Arm I (Doxepin-Placebo) n=69 Participants 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.	Arm II (Placebo-Doxepin) n=71 Participants 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.
Incidence of Using Alternative Analgesics Between 2 and 4 Hours After the Initial Mouthwash At 2 hours after the initial mouthwash	8.8 percentage of patients	2.9 percentage of patients
Incidence of Using Alternative Analgesics Between 2 and 4 Hours After the Initial Mouthwash At 4 hours after the initial mouthwash	16.9 percentage of patients	14.5 percentage of patients

SECONDARY outcome

Timeframe: Up to 9 days

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.

Outcome measures

Outcome measures
Measure	Arm I (Doxepin-Placebo) n=69 Participants 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.	Arm II (Placebo-Doxepin) n=71 Participants 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.
Patient Preference for Continuing Therapy With Oral Doxepin Hydrochloride	77.3 percentage of patients	51.5 percentage of patients

Adverse Events

Arm I (Doxepin-Placebo)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Arm II (Placebo-Doxepin)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Arm I (Doxepin-Placebo) n=74 participants at risk 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.	Arm II (Placebo-Doxepin) n=75 participants at risk 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.
Gastrointestinal disorders Diarrhea	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/75 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Dry mouth	4.1% 3/74 • Number of events 4 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/75 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Dysphagia	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/75 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Mucositis oral	5.4% 4/74 • Number of events 9 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	8.0% 6/75 • Number of events 12 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Nausea	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	1.3% 1/75 • Number of events 2 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Oral pain	2.7% 2/74 • Number of events 5 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	2.7% 2/75 • Number of events 2 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Salivary duct inflammation	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/75 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Vomiting	0.00% 0/74 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	1.3% 1/75 • Number of events 2 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Fatigue	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/75 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Anorexia	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/75 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Dehydration	0.00% 0/74 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	1.3% 1/75 • Number of events 2 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Nervous system disorders Lethargy	0.00% 0/74 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	1.3% 1/75 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Nervous system disorders Somnolence	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	2.7% 2/75 • Number of events 2 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Cough	1.4% 1/74 • Number of events 1 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/75 • Adverse events are assessed during the Active Monitoring Phase at the following time points: at time Dose 1 of study treatment is administered, at time of Dose 2 crossover, during the Optional Continuation Phase, and at the end of the study. All adverse events are collected during the first day; up to 9 days. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.

Additional Information

Robert C. Miller, M.D.

Mayo Clinic

Phone: 507/266-6247

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place