Trial Outcomes & Findings for Four Arm Safety & Efficacy With Antipyrine and Benzocaine Otic Solution in Children With Acute Otitis Media (NCT NCT02037893)

NCT ID: NCT02037893

Last Updated: 2024-08-07

Results Overview

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain. The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 112 participants
• Primary outcome timeframe: Baseline and 1 hour after a single dose
• Results posted on: 2024-08-07

Participant Flow

Participant milestones

Measure	Antipyrine and Benzocaine Otic Solution antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Overall Study STARTED	32	25	27	28
Overall Study COMPLETED	32	25	26	28
Overall Study NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Four Arm Safety & Efficacy With Antipyrine and Benzocaine Otic Solution in Children With Acute Otitis Media

Baseline characteristics by cohort

Measure	Antipyrine and Benzocaine Otic Solution n=32 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=25 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=27 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=28 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Total n=112 Participants Total of all reporting groups
Age, Continuous	4.4 years STANDARD_DEVIATION 3.27 • n=5 Participants	4.4 years STANDARD_DEVIATION 3.36 • n=7 Participants	4.5 years STANDARD_DEVIATION 3.75 • n=5 Participants	3.5 years STANDARD_DEVIATION 3.35 • n=4 Participants	4.2 years STANDARD_DEVIATION 3.41 • n=21 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	44 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	15 Participants n=7 Participants	16 Participants n=5 Participants	18 Participants n=4 Participants	68 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	26 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	19 Participants n=7 Participants	21 Participants n=5 Participants	22 Participants n=4 Participants	85 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	22 Participants n=7 Participants	24 Participants n=5 Participants	24 Participants n=4 Participants	94 Participants n=21 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	32 participants n=5 Participants	25 participants n=7 Participants	27 participants n=5 Participants	28 participants n=4 Participants	112 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and 1 hour after a single dose

Population: Intent-to-Treat population

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=30 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=24 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=22 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=27 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R)	-4.3 units on a scale Standard Deviation 3.43	-5.0 units on a scale Standard Deviation 2.82	-4.6 units on a scale Standard Deviation 2.97	-4.9 units on a scale Standard Deviation 2.13

SECONDARY outcome

Timeframe: Change from Baseline to 15 min post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=31 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=24 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=24 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=28 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R)15 Min Post First Dose	-3.6 units on a scale Standard Error 0.48	-3.6 units on a scale Standard Error 0.54	-3.4 units on a scale Standard Error 0.51	-3.8 units on a scale Standard Error 0.51

SECONDARY outcome

Timeframe: Change from Baseline to 30 min post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=30 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=24 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=24 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=27 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 30 Min Post First Dose	-3.9 units on a scale Standard Error 0.45	-4.3 units on a scale Standard Error 0.51	-4.4 units on a scale Standard Error 0.49	-4.8 units on a scale Standard Error 0.48

SECONDARY outcome

Timeframe: Change from Baseline to 3 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=29 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=22 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=20 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=23 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 3 Hour Post First Dose	-3.4 units on a scale Standard Error 0.47	-3.9 units on a scale Standard Error 0.53	-3.8 units on a scale Standard Error 0.50	-3.5 units on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: Change from Baseline to 6 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=27 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=21 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=19 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=19 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 6 Hours Post First Dose	-3.4 units on a scale Standard Error 0.50	-4.0 units on a scale Standard Error 0.56	-3.9 units on a scale Standard Error 0.54	-3.8 units on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Change from Baseline to 12 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=19 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=16 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=17 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=14 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 12 Hours Post First Dose	-3.9 units on a scale Standard Error 0.53	-4.3 units on a scale Standard Error 0.60	-4.1 units on a scale Standard Error 0.57	-4.0 units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: Change from Baseline to 24 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=29 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=20 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=21 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=22 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 24 Hours Post First Dose	-5.5 units on a scale Standard Error 0.42	-4.4 units on a scale Standard Error 0.48	-4.2 units on a scale Standard Error 0.46	-4.6 units on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Change from Baseline to 36 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=22 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=20 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=19 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=20 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 36 Hours Post First Dose	-5.5 units on a scale Standard Error 0.42	-4.6 units on a scale Standard Error 0.48	-4.4 units on a scale Standard Error 0.46	-5.5 units on a scale Standard Error 0.45

SECONDARY outcome

Timeframe: Change from Baseline to 48 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=30 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=23 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=22 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=26 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 48 Hours Post First Dose	-5.4 units on a scale Standard Error 0.37	-5.3 units on a scale Standard Error 0.42	-4.7 units on a scale Standard Error 0.40	-5.9 units on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: Change from Baseline to 60 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=24 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=21 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=19 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=20 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 60 Hours Post First Dose	-5.4 units on a scale Standard Error 0.33	-5.4 units on a scale Standard Error 0.37	-5.4 units on a scale Standard Error 0.36	-6.2 units on a scale Standard Error 0.36

SECONDARY outcome

Timeframe: Change from Baseline to 72 hour post first dose

Population: The intent-to-treat (ITT) population included all subjects who were randomized to receive treatment and had at least one postscreening efficacy assessment at the timepoint of interest.

The relative change from baseline in pain intensity as measured by changes in FLACC scores or FPS-R scores between baseline and 15 and 30 minutes, and 3, 6, 12, 24, 36, 48, 60, and 72 hours after first dose.

The FLACC was completed by the caregiver to assess pain intensity for subjects aged 2 months to less than 5 years. The FLACC consists of five domains that are rated as 0, 1, or 2 (total scores range from 0 to 10). A lower score indicates lower level of pain.

The FPS-R was completed by the subject aged 5 to 12 years. For this assessment, the subject selected the pain intensity by using faces that show increasing discomfort. Total scores range from 0 to 10. A lower score indicates lower level of pain.

Outcome measures

Measure	Antipyrine and Benzocaine Otic Solution n=30 Participants antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=24 Participants Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=24 Participants benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=26 Participants Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Face, Legs, Activity, Cry, Consolability Scale (FLACC) or Faces Pain Scale Revised (FPS-R) 72 Hours Post First Dose	-5.9 units on a scale Standard Error 0.29	-5.9 units on a scale Standard Error 0.33	-5.4 units on a scale Standard Error 0.32	-6.1 units on a scale Standard Error 0.32

Adverse Events

Antipyrine and Benzocaine Otic Solution

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Antipyrine Otic Solution

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Benzocaine Otic Solution

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Antipyrine and Benzocaine Otic Solution n=32 participants at risk antipyrine 54 mg and benzocaine 14 mg. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine and Benzocaine otic solution: antipyrine 54 mg and benzocaine 14 mg Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Antipyrine Otic Solution n=25 participants at risk Antipyrine 54 mg and glycerine dehydrated to 1.0 mL. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Antipyrine Otic Solution: Antipyrine 54 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Benzocaine Otic Solution n=27 participants at risk benzocaine 14 mg and glycerine dehydrated to 1.0 ml. Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Benzocaine Otic Solution: benzocaine 14 mg and glycerine dehydrated to 1.0 mL Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated	Placebo n=28 participants at risk Placebo otic solution will be glycerin that is dehydrated . Apply drops along the wall of the ear canal until filled and repeating every 3 hours for 24 hours unless the subject is sleeping Placebo Otic solution: Placebo otic solution will be glycerin that is dehydrated
Ear and labyrinth disorders Ear pain	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	3.6% 1/28 • Number of events 1 • Up to 120 hours after first dose
Ear and labyrinth disorders Hypoacisis	0.00% 0/32 • Up to 120 hours after first dose	4.0% 1/25 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Gastrointestinal disorders Diarrhea	0.00% 0/32 • Up to 120 hours after first dose	4.0% 1/25 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Gastrointestinal disorders Nausea	0.00% 0/32 • Up to 120 hours after first dose	4.0% 1/25 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Gastrointestinal disorders Vomiting	3.1% 1/32 • Number of events 1 • Up to 120 hours after first dose	16.0% 4/25 • Number of events 4 • Up to 120 hours after first dose	3.7% 1/27 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
General disorders Application site pain	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	3.7% 1/27 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
General disorders Pyrexia	3.1% 1/32 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Infections and infestations Lice infestation	3.1% 1/32 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Infections and infestations Otitis Media	0.00% 0/32 • Up to 120 hours after first dose	4.0% 1/25 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	3.6% 1/28 • Number of events 1 • Up to 120 hours after first dose
Infections and infestations Otitis Media acute	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	3.6% 1/28 • Number of events 1 • Up to 120 hours after first dose
Infections and infestations Upper respiratory tract infection	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	3.6% 1/28 • Number of events 1 • Up to 120 hours after first dose
Infections and infestations Viral rash	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	3.7% 1/27 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Injury, poisoning and procedural complications Excoriation	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	3.7% 1/27 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Metabolism and nutrition disorders Dehydration	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	3.6% 1/28 • Number of events 1 • Up to 120 hours after first dose
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	3.6% 1/28 • Number of events 1 • Up to 120 hours after first dose
Nervous system disorders Headache	3.1% 1/32 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Nervous system disorders Somnolence	3.1% 1/32 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/32 • Up to 120 hours after first dose	4.0% 1/25 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	3.1% 1/32 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Respiratory, thoracic and mediastinal disorders Rhinorrhea	0.00% 0/32 • Up to 120 hours after first dose	4.0% 1/25 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/27 • Up to 120 hours after first dose	3.6% 1/28 • Number of events 1 • Up to 120 hours after first dose
Skin and subcutaneous tissue disorders Acne	0.00% 0/32 • Up to 120 hours after first dose	0.00% 0/25 • Up to 120 hours after first dose	3.7% 1/27 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/32 • Up to 120 hours after first dose	4.0% 1/25 • Number of events 1 • Up to 120 hours after first dose	3.7% 1/27 • Number of events 1 • Up to 120 hours after first dose	0.00% 0/28 • Up to 120 hours after first dose

Additional Information

Senior Director, Medical and Scientific Affairs

Pernix Therapeutics

Phone: 8007932145

Email: egould@pernixtx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place