Study to Compare Efficacy and Safety of AR01 to a Placebo Solution for Relief of Pain in Acute Otitis Media (AR01007)

A Phase 3, Multicenter, Placebo-controlled, Double-blind, Randomized Study to Compare the Efficacy and Safety of AR01 Otic Solution to a Placebo Solution for Relief of Pain in Acute Otitis Media Subjects Aged 2 Months to 19 Years

Children ages 2 months to less than 19 years old, who have been diagnosed with a middle ear infection may receive either medicated ear drops (AR01) or glycerin (placebo) ear drops. The patient or caregiver will measure the amount of ear pain before and after the ear drops to establish if the medicated ear drops decrease the amount of pain more than the placebo ear drops. The subject may leave the clinic 60 minutes after the first dose. The ear drops can be used up to 4 days, as needed for ear pain.

Study Overview

• Status: Terminated
• Conditions: Acute Otitis Media
• Intervention / Treatment: Drug: AR01; Drug: Placebo Comparator

Detailed Description

The study involves the initial clinic visit, using the ear drops at home and keeping a diary about the ear pain experienced and medications taken. The patient will return to the clinic 4 days later for evaluation and to return the ear drops and diary. The clinic staff will call to follow-up about the patient's condition seven days after the initial visit.

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Clinical Research Consortium Arizona
  • California
    • Bakersfield, California, United States, 93301
      • Kern Allergy and Medical Research, Inc
    • Fresno, California, United States, 93720
      • Central California Research
  • Florida
    • Naples, Florida, United States, 34102
      • Pharma Research International, Inc
    • St. Petersburg, Florida, United States, 33710
      • SCORE Physician Alliance, LLC
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric / Adult Research
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Pioneer Clinical Research, LLC
    • Omaha, Nebraska, United States, 68130
      • Omaha ENT Clinic
  • New York
    • Utica, New York, United States, 13502
      • Children's Health Center / St. Elizabeth Medical Center
    • Valley Stream, New York, United States, 11580
      • Valley Stream Pediatrics
  • North Carolina
    • Clyde, North Carolina, United States, 39721
      • Haywood pediatric and Adolescent Medicine Group, PA
  • Ohio
    • Cinncinati, Ohio, United States, 45246
      • Sterling Research Group, Ltd
    • Columbus, Ohio, United States, 43207
      • Central Ohio Clinical Research
    • Columbus, Ohio, United States, 43214
      • Urgent Care Specialists Hometown Urgent Care
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Carolina Ear, Nose & Throat Clinic
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • PMG Research of Bristol
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Utah
    • Layton, Utah, United States, 84041
      • Tanner Clinic
    • Salt Lake City, Utah, United States, 84121
      • Foothill Family Clinic South
    • Salt Lake City, Utah, United States, 84121
      • Heartland Research Associates LLC - Augusta
  • Virginia
    • Alexandria, Virginia, United States, 22302
      • Van Dorn Pediatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects 2 mo. to < 19 yrs of age, with signs and symptoms of acute otitis media (AOM), with moderate to severe pain (current episode 2 wks duration). Moderate to severe pain is defined as a score of 5 (on a scale of 0 - 10) on the FAECC pain scale as evaluated by a trained clinical staff or 6 (on a scale of 0 - 10) on the FPS-R as evaluated by the subject. Moderate to severe pain criteria must be met at eligibility and the pre-dose pain assessment.
• Males or non-pregnant, non-lactating females.
• The subject's caregiver must have read and signed the written informed consent (including assent from subjects 18 yrs as applicable according to Investigational review board (IRB) guidelines) prior to study participation. Subjects 18 yrs old must have read and signed the written informed consent prior to study participation.
• Normally active and otherwise judged to be in good health on the basis of medical history and limited physical examination.
• Females of childbearing potential must have a urine pregnancy test at the randomization visit with negative results returned prior to randomization.

Exclusion Criteria

• Perforated tympanic membrane, history of a perforated tympanic membrane in the last 6 months, or if a perforated tympanic membrane could not be ruled out by speculum examination, impedance testing tympanometry, pneumatic otoscopy, or Valsalva maneuver. Subjects who are subsequently diagnosed with a perforated membrane during treatment are to be discontinued immediately. Subjects with tympanostomy tubes are not allowed.
• Acute or chronic otitis externa.
• Chronic otitis media (refers to current episode 2 wks).
• Seborrheic dermatitis involving the affected external ear canal or pinna.
• Any otic, topical, or systemic antibiotic received within 14 days prior to study entry (topical or systemic antibiotics for acne will be allowed on a chronic basis for subjects who have been on a stable dose for at least 14 days prior to entry).
• Any topical drying agent or over-the-counter therapy for otitis media received within 36 hrs prior to enrollment.
• Known hypersensitivity to drug or similar compounds including any of the inactive ingredients.
• Subjects receiving medication on a chronic basis for pain (including steroidal or non-steroidal anti-inflammatory drugs) who have not been on a stable dose for at least 1 month prior to entry into the study.
• Clinically significant mental illness that may interfere with the conduct of the study (determined by Investigator).
• Exposure to any investigational agent within 30 days prior to study entry.
• Previous enrollment in this study.
• Subject/caregiver has a condition the Investigator believes would interfere with the ability to provide consent or assent (age-appropriate) or comply with study instructions, or that might confound the interpretation of the study results, or put the subject at undue risk.
• Subject has a glucose 6-phosphate dehydrogenase deficiency or is taking concomitant medications associated with methemoglobinemia (such as nitrates or nitrites; aniline dyes; or medications, including lidocaine, prilocaine, phenazopyridine hydrochloride [Pyridium], and others).
• Subject shows clinical signs of anemia. The absolute amount of deoxygenated or abnormal hemoglobin (rather than its percentage) is required for cyanosis to be clinically evident. Subjects with moderate-to-severe anemia may not appear cyanotic, even with elevated percentages of deoxygenated or abnormal hemoglobins.
• Subject has congenital (i.e., hereditary) methemoglobinemia.
• Subject has a recent history of acute gastroenteritis within 14 days prior to study entry.
• Subject exhibits clinical signs of methemoglobinemia, such as unexplained bluish coloring of skin, fatigue, shortness of breath, failure to thrive, and headache.
• Subjects 5 to <19 yrs old who are unable to satisfactorily complete FPS-R screening test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: AR01 - Topical Otic Solution; Topical ear drops The dosing regimen is 5-10 drops every hour as needed for ear pain, not to exceed 10 mL of solution per ear in a 24-hour period	Drug: AR01; drops administered as needed for pain; Other Names: benzocaine
PLACEBO_COMPARATOR: Placebo Comparator; Topical ear drops Glycerin ear drops-The dosing regimen is 5-10 drops every hour as needed for ear pain, not to exceed 10 mL of solution per ear in a 24-hour period.	Drug: Placebo Comparator; Glycerin ear drops (placebo) drops administered as needed for ear pain; Other Names: Glycerin ear drops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete ear pain relief	The proportion of subjects with complete pain relief (score of 0 on Face, Activity, Ears, Cry, Consolability tool (FAECC) as measured by the Assigned Clinical Assessor or Faces Pain Scale-Revised (FPS-R) as measured by the subject prior to any analgesic/antipyretic use) at or prior to 60 minutes post baseline dose.	At or prior to 60 minutes post baseline dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with complete ear pain relief	The proportion of subjects with complete ear pain relief (score of 0 on FAECC or FPS-R prior to any analgesic/antipyretic use) at or prior to 10, 20, 30, 45, and 60 minutes post baseline dose.	at or prior to 10, 20, 30, 45, and 60 minutes post baseline dose
The percent change in FPS-R and FAECC pain scores from baseline to post dose scores		measured at 10, 20, 30, 45, and 60 minutes post baseline dose
time to complete ear pain relief (score of 0 on pain scales)	The time to complete pain relief (score of 0 on FAECC or FPS-R prior to any analgesic/antipyretic use), in minutes.	10, 20, 30, 45, and 60 minutes post baseline dose
Sum of pain intensity differences (SPID) using FPS-R and FAECC pain scores		scores at pre-dose and 60 minutes post dose
Time from baseline to in-clinic use of analgesic/antipyretic to relief ear pain		60 minutes
The number of subjects who receive analgesic/antipyretic medications for relief of ear pain during the clinic visit		measured at or prior to 10, 20, 30, 45, and 60 minutes post baseline
Number of adverse events reported as a measure of safety and tolerability		up to 30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from complete ear pain relief (score of 0 on FAECC or FPS-R) to a pain event using the home use data	A pain event may include any or all of the following: analgesic/antipyretic use, a FAECC score ≥5 or FPS-R score ≥6, and study withdrawal due to AOM, treatment, or the study itself.	up to 4 Days (± 1)
Relation between Analgesic/antipyretic use and study medication use during the In-Home Use period at or prior to 15, 30, and 60 minutes	Dates and times of analgesic/antipyretic use from will be compared with the dates and times of home use of study medication to create the use or non-use outcome for each time point.	at or prior to 15, 30, and 60 minutes baseline study medication dose and up to 4 Days (± 1)

Collaborators and Investigators

• Sponsor: Arbor Pharmaceuticals, Inc.
• Investigators: Study Chair: Laurence J Downey, MD, Arbor Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: January 16, 2014
• First Submitted That Met QC Criteria: February 26, 2014
• First Posted (ESTIMATE): February 28, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Pain; Acute Otitis Media; Ear Pain; Ear Ache; Ear infection; middle ear infection
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Benzocaine
• Other Study ID Numbers: AR01.007