Trial Outcomes & Findings for Evaluate Analgesic / Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain (NCT NCT01495858)

Results Overview

WASO was defined as Total wake time (in minutes) after sleep onset during the 10 hours in-bed period as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

267 participants

Primary outcome timeframe

Up to 10 hours

Results posted on

2015-06-08

Participant Flow

Participant milestones

Participant milestones
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Overall Study STARTED	107	106	54
Overall Study COMPLETED	107	106	54
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluate Analgesic / Sedative Efficacy of Naproxen Sodium and Diphenhydramine in Patients With Postsurgical Dental Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.	Total n=267 Participants Total of all reporting groups
Age, Continuous	21.4 Years STANDARD_DEVIATION 5.55 • n=93 Participants	21.3 Years STANDARD_DEVIATION 5.27 • n=4 Participants	20.8 Years STANDARD_DEVIATION 4.64 • n=27 Participants	21.2 Years STANDARD_DEVIATION 5.25 • n=483 Participants
Sex: Female, Male Female	72 Participants n=93 Participants	64 Participants n=4 Participants	37 Participants n=27 Participants	173 Participants n=483 Participants
Sex: Female, Male Male	35 Participants n=93 Participants	42 Participants n=4 Participants	17 Participants n=27 Participants	94 Participants n=483 Participants
Baseline Categorical Pain Rating Scale No pain	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Baseline Categorical Pain Rating Scale Mild pain	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Baseline Categorical Pain Rating Scale Moderate pain	69 Participants n=93 Participants	63 Participants n=4 Participants	28 Participants n=27 Participants	160 Participants n=483 Participants
Baseline Categorical Pain Rating Scale Severe pain	38 Participants n=93 Participants	43 Participants n=4 Participants	26 Participants n=27 Participants	107 Participants n=483 Participants

PRIMARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population

WASO was defined as Total wake time (in minutes) after sleep onset during the 10 hours in-bed period as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects.

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Wake Time After Sleep Onset (WASO) Measured by Actigraphy	155.25 Minutes Interval 121.57 to 188.93	180.08 Minutes Interval 146.36 to 213.8	364.83 Minutes Interval 317.52 to 412.15

PRIMARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population

Sleep latency was defined as the time to sleep onset from the time of dosing as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects.

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Sleep Latency Measured by Actigraphy	23.50 Minutes Interval 18.0 to 28.0	16.75 Minutes Interval 13.5 to 25.0	27.50 Minutes Interval 16.0 to 36.5

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population

Total time spent sleeping (not to exceed 600 minutes) during the in-bed period as measured by actigraphy. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects.

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Total Sleep Time Measured by Actigraphy	418.66 Minutes Interval 385.05 to 452.28	392.38 Minutes Interval 358.72 to 426.03	206.61 Minutes Interval 159.39 to 253.84

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population

Sleep efficiency was calculated as (total sleep time/total time in-bed time) × 100; total in-bed time was fixed at 10 hours. Actigraphy is a non-intrusive tool that measures an individual's movement during sleep. Actigraphy was used to obtain data in discriminating between sleep and wake states in the subjects.

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Sleep Efficiency Measured by Actigraphy	69.777 Percent of sleep time during in-bed time Interval 64.175 to 75.38	65.396 Percent of sleep time during in-bed time Interval 59.787 to 71.006	34.436 Percent of sleep time during in-bed time Interval 26.566 to 42.306

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

The Global Assessment of Investigational Product as a Sleep-Aid was rated using a 5-point categorical scale for which the potential response was poor (0), fair, (1), good (2), very good (3), or excellent (4).

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=85 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=79 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=19 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Global Assessment of Investigational Product as a Sleep Aid 0 = Poor	2 Participants	13 Participants	1 Participants
Global Assessment of Investigational Product as a Sleep Aid 1 = Fair	12 Participants	24 Participants	7 Participants
Global Assessment of Investigational Product as a Sleep Aid 2 = Good	37 Participants	24 Participants	2 Participants
Global Assessment of Investigational Product as a Sleep Aid 3 = Very good	23 Participants	13 Participants	8 Participants
Global Assessment of Investigational Product as a Sleep Aid 4 = Excellent	11 Participants	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to the following question: How was your sleep? very poor (1); rather poor (2); neither poor nor good (3); rather good (4); very good (5)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=102 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Karolinska Sleep Diary - Sleep Quality 1 = Very poor	1 Participants	3 Participants	9 Participants
Karolinska Sleep Diary - Sleep Quality 2 = Rather poor	12 Participants	22 Participants	11 Participants
Karolinska Sleep Diary - Sleep Quality 3 = Neither poor nor good	33 Participants	31 Participants	9 Participants
Karolinska Sleep Diary - Sleep Quality 4 = Rather good	47 Participants	36 Participants	12 Participants
Karolinska Sleep Diary - Sleep Quality 5 = Very good	9 Participants	10 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to the following question: How calm was your sleep? very restless (1); rather restless (2); neither restless nor calm (3); rather calm (4); very calm (5)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=102 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Karolinska Sleep Diary - Calmness of Sleep 1 = Very restless	1 Participants	3 Participants	5 Participants
Karolinska Sleep Diary - Calmness of Sleep 2 = Rather restless	26 Participants	29 Participants	17 Participants
Karolinska Sleep Diary - Calmness of Sleep 3 = Neither restless nor calm	18 Participants	24 Participants	5 Participants
Karolinska Sleep Diary - Calmness of Sleep 4 = Rather calm	48 Participants	42 Participants	13 Participants
Karolinska Sleep Diary - Calmness of Sleep 5 = Very calm	9 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to the following question: How easy was it to fall asleep? very difficult (1); rather difficult (2); neither difficult nor easy (3); rather easy (4); very easy (5)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=102 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Karolinska Sleep Diary - Easiness to Fall Asleep 1 = Very difficult	3 Participants	8 Participants	9 Participants
Karolinska Sleep Diary - Easiness to Fall Asleep 2 = Rather difficult	29 Participants	33 Participants	6 Participants
Karolinska Sleep Diary - Easiness to Fall Asleep 3 = Neither difficult nor easy	22 Participants	27 Participants	14 Participants
Karolinska Sleep Diary - Easiness to Fall Asleep 4 = Rather easy	36 Participants	23 Participants	12 Participants
Karolinska Sleep Diary - Easiness to Fall Asleep 5 = Very easy	12 Participants	11 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to the following question : Premature awakening? woke up much too early (1); woke up somewhat too early (2); no (3)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=102 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Karolinska Sleep Diary - Premature Awakening 1 = Woke up much too early	24 Participants	31 Participants	21 Participants
Karolinska Sleep Diary - Premature Awakening 2 = Woke up somewhat too early	45 Participants	52 Participants	11 Participants
Karolinska Sleep Diary - Premature Awakening 3 = No	33 Participants	19 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to the following question: Ease of awakening? (1) very difficult; (2) rather difficult; (3) neither difficult nor easy; (4) rather easy; very easy (5)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=102 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Karolinska Sleep Diary - Ease of Awakening 1 = Very difficult	0 Participants	3 Participants	0 Participants
Karolinska Sleep Diary - Ease of Awakening 2 = Rather difficult	1 Participants	0 Participants	2 Participants
Karolinska Sleep Diary - Ease of Awakening 3 = Neither difficult nor easy	17 Participants	16 Participants	5 Participants
Karolinska Sleep Diary - Ease of Awakening 4 = Rather easy	56 Participants	53 Participants	14 Participants
Karolinska Sleep Diary - Ease of Awakening 5 = Very easy	28 Participants	30 Participants	23 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to the following question: Well Rested? not rested at all (1); somewhat unrested (2); completely rested (3)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=102 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Karolinska Sleep Diary - Well Rested 1 = Not rested at all	7 Participants	9 Participants	13 Participants
Karolinska Sleep Diary - Well Rested 2 = Somewhat unrested	53 Participants	55 Participants	17 Participants
Karolinska Sleep Diary - Well Rested 3 = Completely rested	42 Participants	38 Participants	14 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to the following question: Did you get enough (sufficient) sleep? no, definitely too little (1); no, much too little (2); no, somewhat too little (3); yes, almost enough (4); yes, definitely enough (5)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=102 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Karolinska Sleep Diary - Sufficient Sleep 2 = No, much too little	8 Participants	10 Participants	6 Participants
Karolinska Sleep Diary - Sufficient Sleep 1 = No, definitely too little	2 Participants	10 Participants	13 Participants
Karolinska Sleep Diary - Sufficient Sleep 3 = No, somewhat too little	18 Participants	27 Participants	8 Participants
Karolinska Sleep Diary - Sufficient Sleep 4 = Yes, almost enough	52 Participants	34 Participants	11 Participants
Karolinska Sleep Diary - Sufficient Sleep 5 = Yes, definitely enough	22 Participants	21 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subject evaluated sleep quality on a 10-point scale, where 1 was poor and 10 was excellent.

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=101 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Subjective Sleep Questionnaire - Quality of Your Sleep Last Night	6.5 Scores on a scale Standard Deviation 1.95	5.8 Scores on a scale Standard Deviation 2.11	4.9 Scores on a scale Standard Deviation 3.04

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to Refreshing nature of sleep (10-point scale, where 1 was not refreshing and 10 was very refreshing)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=101 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Subjective Sleep Questionnaire - Refreshing Nature of Your Sleep Last Night	6.6 Scores on a scale Standard Deviation 2.15	5.7 Scores on a scale Standard Deviation 2.20	4.6 Scores on a scale Standard Deviation 2.85

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to Estimate of how long it took to fall asleep (minutes)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=101 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Subjective Sleep Questionnaire - Time to Fall Asleep Last Night	39.5 Minutes Standard Deviation 36.63	40.2 Minutes Standard Deviation 38.10	40.0 Minutes Standard Deviation 42.66

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

Subjects responded to Estimate of the amount of time the subject was awake from the time he or she fell asleep until the time he or she got out of bed (hours and minutes)

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=102 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=101 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=44 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Subjective Sleep Questionnaire - Number of Minutes You Think That You Were Awake From the Time You Fell Asleep Until the Time You Got Out of Bed	111.1 Minutes Standard Deviation 121.86	144.8 Minutes Standard Deviation 125.58	98.4 Minutes Standard Deviation 89.71

SECONDARY outcome

Timeframe: Baseline and up to 10 hours

Population: ITT (Intent to Treat) Population

Pain Severity was collected on a 4-point categorical scale: 0=no pain, 1=mild pain, 2=moderate pain, 4=severe pain

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Change From Baseline in Pain Intensity	2.4 Scores on a scale Standard Deviation 0.48	2.4 Scores on a scale Standard Deviation 0.49	2.5 Scores on a scale Standard Deviation 0.50

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population

The Pain Relief Rating Scale was a 5-point categorical scale which included the following possible responses to the request to finish statement "Overall, the relief from my starting pain was": no relief (0); a little relief (1); some relief (2); a lot of relief (3); complete relief (4).

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Overall Rating of Pain Relief 0 = No relief	24 Participants	30 Participants	35 Participants
Overall Rating of Pain Relief 1 = A little relief	5 Participants	3 Participants	4 Participants
Overall Rating of Pain Relief 2 = Some relief	10 Participants	15 Participants	5 Participants
Overall Rating of Pain Relief 3 = A lot of relief	47 Participants	37 Participants	8 Participants
Overall Rating of Pain Relief 4 = Complete relief	21 Participants	21 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population

If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Time to Rescue Medication	NA Minutes Technically the data is not computable due to insufficient number of events	NA Minutes Technically the data is not computable due to insufficient number of events	146.50 Minutes Interval 118.0 to 314.0

SECONDARY outcome

Timeframe: Up to 10 hours

Population: Safety Population

If rescue medication was taken by a subject for pain, then the time of rescue medication administration was recorded

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 600 minutes	24 participants	30 participants	35 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 60 minutes	0 participants	1 participants	0 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 120 minutes	9 participants	12 participants	21 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 180 minutes	14 participants	13 participants	29 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 240 minutes	15 participants	17 participants	32 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 300 minutes	16 participants	23 participants	33 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 360 minutes	17 participants	25 participants	34 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 420 minutes	21 participants	26 participants	35 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 480 minutes	22 participants	28 participants	35 participants
Cumulative Proportion of Participants Taking Rescue Medication by Hour ≤ 540 minutes	24 participants	30 participants	35 participants

SECONDARY outcome

Timeframe: Up to 10 hours

Population: ITT (Intent to Treat) Population with available data (missing values were not imputed)

The Global Assessment of Investigational Product as a Pain Reliever was a 5- point categorical scale which included the following possible responses: poor (0); fair (1); good (2); very good (3); excellent (4).

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=85 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=79 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=19 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Global Assessment of Investigational Product as a Pain Reliever 0 = Poor	1 Participants	1 Participants	1 Participants
Global Assessment of Investigational Product as a Pain Reliever 1 = Fair	4 Participants	3 Participants	5 Participants
Global Assessment of Investigational Product as a Pain Reliever 2 = Good	22 Participants	25 Participants	3 Participants
Global Assessment of Investigational Product as a Pain Reliever 3 = Very good	40 Participants	38 Participants	9 Participants
Global Assessment of Investigational Product as a Pain Reliever 4 = Excellent	18 Participants	12 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and day 2

Population: Safety Population

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Vital Signs: Mean Change From Baseline in Systolic Blood Pressure at Day 2	-1.3 mmHg Standard Deviation 12.65	-0.6 mmHg Standard Deviation 13.51	2.2 mmHg Standard Deviation 11.77

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Day 2

Population: Safety Population

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Vital Signs: Mean Change From Baseline in Diastolic Blood Pressure at Day 2	0.7 mmHg Standard Deviation 10.58	-0.2 mmHg Standard Deviation 8.42	2.1 mmHg Standard Deviation 8.83

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and day 2

Population: Safety Population

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Vital Signs: Mean Change From Baseline in Pulse Rate at Day 2	1.0 Beats/min Standard Deviation 10.57	-0.1 Beats/min Standard Deviation 11.94	4.7 Beats/min Standard Deviation 12.65

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and day 2

Population: Safety Population

Outcome measures

Outcome measures
Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 Participants Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally.	Naproxen Sodium 440 mg (BAYH6689) n=106 Participants Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally.	DPH 50 mg n=54 Participants Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Vital Signs: Mean Change From Baseline in Respiratory Rate at Day 2	-1.4 Breaths/min Standard Deviation 3.12	-1.2 Breaths/min Standard Deviation 2.97	-0.3 Breaths/min Standard Deviation 2.70

Adverse Events

Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Naproxen Sodium 440 mg (BAYH6689)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

DPH 50 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Therapeutic Area Head

BAYER

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Naproxen Sodium 440 mg / DPH 25 mg (BAY98-7111) n=107 participants at risk Participants received one tablet of Naproxen Sodium 220 mg / Diphenhydramine hydrochloride (DPH) 25 mg and one tablet of Naproxen Sodium 220 mg, single dose, orally	Naproxen Sodium 440 mg (BAYH6689) n=106 participants at risk Participants received two tablets of Naproxen Sodium 220 mg, single dose, orally	DPH 50 mg n=54 participants at risk Participants received two tablets of Diphenhydramine hydrochloride (DPH) 25 mg, single dose, orally.
Ear and labyrinth disorders Deafness	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Ear and labyrinth disorders Tinnitus	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.94% 1/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Eye disorders Vision blurred	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Gastrointestinal disorders Nausea	5.6% 6/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	3.8% 4/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	3.7% 2/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Gastrointestinal disorders Vomiting	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.94% 1/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
General disorders Chest discomfort	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
General disorders Feeling hot	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.94% 1/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
General disorders Feeling jittery	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.94% 1/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Injury, poisoning and procedural complications Procedural complication	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Investigations Blood pressure increased	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Investigations Cardiac murmur	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Nervous system disorders Dizziness	8.4% 9/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	8.5% 9/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	3.7% 2/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Nervous system disorders Headache	5.6% 6/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	2.8% 3/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	18.5% 10/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Nervous system disorders Hypoaesthesia	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Nervous system disorders Syncope	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.94% 1/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Renal and urinary disorders Pollakiuria	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Skin and subcutaneous tissue disorders Cold sweat	2.8% 3/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Skin and subcutaneous tissue disorders Hyperhidrosis	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Skin and subcutaneous tissue disorders Pruritus	0.93% 1/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).
Vascular disorders Flushing	0.00% 0/107 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	0.00% 0/106 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).	1.9% 1/54 • Treatment emergent adverse events (TEAEs) were collected from the date of the first dose of study drug in the treatment period for 2 days, or for 30 days after the last study drug administration if they were serious adverse events (SAEs).