Clinical trial NCT02074007: Study to Compare Efficacy and Safety of AR01 to a Placebo Solution for Relief of Pain in Acute Otitis Media (AR01007)
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: TERMINATED
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: 2014-02-28
Enrollment: 178
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 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.

Primary outcomes:
measure: Complete ear pain relief
timeFrame: At or prior to 60 minutes post baseline dose
Secondary outcomes:
measure: time to complete ear pain relief (score of 0 on pain scales)
timeFrame: 10, 20, 30, 45, and 60 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 differences (SPID) using FPS-R and FAECC pain scores
timeFrame: scores at pre-dose and 60 minutes post dose
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
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 Use period at or prior to 15, 30, and 60 minutes
timeFrame: at or prior to 15, 30, and 60 minutes baseline study medication dose and up to 4 Days (± 1)
Locations:
city: Phoenix
country: United States
facility: Clinical Research Consortium Arizona
state: Arizona
city: Bakersfield
country: United States
facility: Kern Allergy and Medical Research, Inc
state: California
city: Fresno
country: United States
facility: Central California Research
state: California
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: Bardstown
country: United States
facility: Kentucky Pediatric / Adult Research
state: Kentucky
city: Bellevue
country: United States
facility: Pioneer Clinical Research, LLC
state: Nebraska
city: Omaha
country: United States
facility: Omaha ENT Clinic
state: Nebraska
city: Utica
country: United States
facility: Children's Health Center / St. Elizabeth Medical Center
state: New York
city: Valley Stream
country: United States
facility: Valley Stream Pediatrics
state: New York
city: Clyde
country: United States
facility: Haywood pediatric and Adolescent Medicine Group, PA
state: North Carolina
city: Cinncinati
country: United States
facility: Sterling Research Group, LTD
state: Ohio
city: Columbus
country: United States
facility: Central Ohio Clinical Research
state: Ohio
city: Columbus
country: United States
facility: Urgent Care Specialists Hometown Urgent Care
state: Ohio
city: Orangeburg
country: United States
facility: Carolina Ear, Nose & Throat Clinic
state: South Carolina
city: Bristol
country: United States
facility: PMG Research of Bristol
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Layton
country: United States
facility: Tanner Clinic
state: Utah
city: Salt Lake City
country: United States
facility: Foothill Family Clinic South
state: Utah
city: Salt Lake City
country: United States
facility: Heartland Research Associates LLC - Augusta
state: Utah
city: Alexandria
country: United States
facility: Van Dorn Pediatrics
state: Virginia
Study officials:
affiliation: Arbor Pharmaceuticals, Inc.
name: Laurence J Downey, MD
role: STUDY_CHAIR
References: