Clinical trial NCT02044341: Phase 3 Study to Compare the Efficacy and Safety of AR01 to a Placebo Solution for Relief of Pain in Acute Otitis Media
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Otitis Media
Keywords: Acute Otitis Media
Pain
Ear Pain
Ear Ache
Ear infection
middle ear infection
Lead sponsor: Arbor Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-01-24
Enrollment: 304
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* Subjects 2 mo. to \< 19 yrs of age, with signs and symptoms of 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.

Primary outcomes:
measure: Complete ear pain relief
timeFrame: At or prior to 60 minutes post baseline dose
Secondary outcomes:
measure: time to complete pain relief (score of 0 on pain scales)
timeFrame: 10, 20, 30, 45, and a60 minutes post baseline dose
measure: The proportion of subjects with complete ear pain relief
timeFrame: at or prior to 10, 20, 30, 45, and 60 minutes post baseline dose
measure: The percent change in FPS-R and FAECC pain scores from baseline to post dose scores
timeFrame: measured at 10, 20, 30, 45, and 60 minutes post baseline dose
measure: Sum of pain intensity (SPID) using FPS-R and FAECC pain scores
timeFrame: measured from baseline (pre-dose) to 60 minutes
measure: Time from baseline to in-clinic use of analgesic/antipyretic to relief ear pain
timeFrame: 60 Minutes
measure: The number of subjects who receive analgesic/antipyretic medications for relief of ear pain during the clinic visit
timeFrame: measured at or prior to 10, 20, 30, 45, and 60 minutes post baseline dose
measure: Number of adverse events reported as a measure of safety and tolerability
timeFrame: up to 30 days
Other outcomes:
measure: Time from complete ear pain relief (score of 0 on FAECC or FPS-R) to a pain event using the home use data
timeFrame: up to 4 Days (± 1)
measure: Relation between analgesic/antipyretic use and study medication use during the in-home period
timeFrame: at or prior to 15, 30, and 60 minutes baseline study medication dose and up to 4 Days (± 1)
Locations:
city: Sheffield
country: United States
facility: Shoals Medical Trials, Inc.
state: Alabama
city: Tuscon
country: United States
facility: SC Clinical Research, Inc
state: Arizona
city: Jonesboro
country: United States
facility: NEA Baptist Clinic
state: Arkansas
city: Bellflower
country: United States
facility: So Cal Clinical Research Group
state: California
city: Fountain Valley
country: United States
facility: Southland Clinical Research Center
state: California
city: Madera
country: United States
facility: Madera Family Medical Group
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Health Partners /Clinical Research Advantag
state: Colorado
city: Naples
country: United States
facility: Pharma Research International, Inc
state: Florida
city: St. Petersburg
country: United States
facility: SCORE Physician Alliance, LLC
state: Florida
city: West Des Moines
country: United States
facility: The Iowa Clinic, Pc
state: Iowa
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric / Adult Research
state: Kentucky
city: Louisville
country: United States
facility: Brownsboro Park Pediatrics
state: Kentucky
city: Nicholasville
country: United States
facility: Michael W. Simon, MD, PSC
state: Kentucky
city: Silver Spring
country: United States
facility: Virgo-Carter Pediatrics
state: Maryland
city: Minneapolis
country: United States
facility: Hennepin County Medical Center -Department of Emergency Medicine
state: Minnesota
city: Las Vegas
country: United States
facility: Clinical Research Center
state: Nevada
city: Valley Stream
country: United States
facility: Valley Stream Pediatrics
state: New York
city: Asheboro
country: United States
facility: White Oak Family Physicians
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Children's Hospital - General Pediatrics and Adolescent Medicine
state: North Carolina
city: Dayton
country: United States
facility: Hometown Urgent Care and Research Center (Dayton)
state: Ohio
city: Bristol
country: United States
facility: PMG Research of Bristol
state: Tennessee
city: Byran
country: United States
facility: DiscoveResearch, Inc.
state: Texas
city: Dallas
country: United States
facility: Research Across America - Dallas
state: Texas
city: Tomball
country: United States
facility: Pediatric Healthcare of Northwest Houston, PA
state: Texas
city: Jordan
country: United States
facility: J. Lewis Research, Inc/Jordan River Family Medicine
state: Utah
city: Salt Lake City
country: United States
facility: FirstMed
state: Utah
city: Salt Lake City
country: United States
facility: Lewis Research, Inc/Foothill Family Clinic
state: Utah
city: Syracuse
country: United States
facility: Wee Care Pediatrics
state: Utah
Study officials:
affiliation: Arbor Pharmaceuticals, LLC
name: Laurence J Downey, MD
role: STUDY_CHAIR
References: