Phase 3 Study to Compare the Efficacy and Safety of AR01 to a Placebo Solution for Relief of Pain in Acute Otitis Media

Acute Otitis Media Clinical Trial

— AR01006  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02044341
• Other study ID #: AR01.006
• Status: Completed
• Phase: Phase 3
• First received: January 22, 2014
• Last updated: March 19, 2015
• Start date: December 2013
• Est. completion date: March 2014

Study information

• Verified date: March 2015
• Source: Arbor Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Months to 18 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Otitis Media
• Otitis
• Otitis Media

Intervention

Drug:
• AR01
drops administered an needed for pain
• Glycerin ear drops
placebo drops administered for ear pain

Locations

Country	Name	City	State
United States	White Oak Family Physicians	Asheboro	North Carolina
United States	Kentucky Pediatric / Adult Research	Bardstown	Kentucky
United States	So Cal Clinical Research Group	Bellflower	California
United States	PMG Research of Bristol	Bristol	Tennessee
United States	DiscoveResearch, Inc.	Byran	Texas
United States	UNC Children's Hospital - General Pediatrics and Adolescent Medicine	Chapel Hill	North Carolina
United States	Colorado Springs Health Partners /Clinical Research Advantag	Colorado Springs	Colorado
United States	Research Across America - Dallas	Dallas	Texas
United States	Hometown Urgent Care and Research Center (Dayton)	Dayton	Ohio
United States	Southland Clinical Research Center	Fountain Valley	California
United States	NEA Baptist Clinic	Jonesboro	Arkansas
United States	J. Lewis Research, Inc/Jordan River Family Medicine	Jordan	Utah
United States	Clinical Research Center	Las Vegas	Nevada
United States	Brownsboro Park Pediatrics	Louisville	Kentucky
United States	Madera Family Medical Group	Madera	California
United States	Hennepin County Medical Center -Department of Emergency Medicine	Minneapolis	Minnesota
United States	Pharma Research International, Inc	Naples	Florida
United States	Michael W. Simon, MD, PSC	Nicholasville	Kentucky
United States	FirstMed	Salt Lake City	Utah
United States	Lewis Research, Inc/Foothill Family Clinic	Salt Lake City	Utah
United States	Shoals Medical Trials, Inc.	Sheffield	Alabama
United States	Virgo-Carter Pediatrics	Silver Spring	Maryland
United States	SCORE Physician Alliance, LLC	St. Petersburg	Florida
United States	Wee Care Pediatrics	Syracuse	Utah
United States	Pediatric Healthcare of Northwest Houston, PA	Tomball	Texas
United States	SC Clinical Research, Inc	Tuscon	Arizona
United States	Valley Stream Pediatrics	Valley Stream	New York
United States	The Iowa Clinic, Pc	West Des Moines	Iowa
United States	Heartland Research Associates, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Arbor Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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 analgesic/antipyretic use, a FAECC score of >/= 5 or FPS-R score of >/= 6, or study withdrawal due to AOM, treatment, or the study itself	up to 4 Days (± 1)	No
Other	Relation between analgesic/antipyretic use and study medication use during the in-home period	Dates and times of analgesic/antipyretic use 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)	No
Primary	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	No
Secondary	time to complete 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 a60 minutes post baseline dose	No
Secondary	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	No
Secondary	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	No
Secondary	Sum of pain intensity (SPID) using FPS-R and FAECC pain scores		measured from baseline (pre-dose) to 60 minutes	No
Secondary	Time from baseline to in-clinic use of analgesic/antipyretic to relief ear pain		60 Minutes	No
Secondary	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 dose	No
Secondary	Number of adverse events reported as a measure of safety and tolerability	measured by treatment-emergent adverse events (AEs), concomitant medications, vital signs (pulse, temperature, and respiratory rate), abbreviated physical examination (head, ears, eyes, nose and throat and chest), external ear canal and pinna for signs of local tissue toxicity, such as rash, urticaria, local burning or stinging, skin discoloration, swelling, itching, and severe redness, and an assessment for signs of methemoglobinemia (i.e., unexplained bluish coloring of skin, fatigue, shortness of breath, failure to thrive, and headache).	up to 30 days	Yes