Pediatric Pharmacokinetic (PK) Study of EXE844 Otic Suspension in Otitis Media at the Time of Tympanostomy Tube Insertion (OMTT)

Study Overview
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Brief Summary
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The purpose of this study is to describe the pharmacokinetics (PK) of EXE844 Sterile Otic Suspension, 0.3% following a single bilateral ototopical dose in pediatric subjects, immediately after bilateral tympanostomy tube surgery.

Official Title
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An Open-Label, Single-Dose, Pharmacokinetic Study of EXE844 Sterile Otic Suspension, 0.3% in Pediatric Subjects Following Tympanostomy Tube Surgery

Conditions
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Otitis Media With Effusion in Children, Otitis Media Recurrent

Intervention / Treatment
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* Drug: EXE844 Sterile Otic Suspension, 0.3%
* Procedure: Tympanostomy Tube Insertion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recurrent acute otitis media (RAOM) or chronic otitis media with effusion (COME) and eligible for bilateral myringotomy and tympanostomy tube insertion; Legally Authorized Representative (LAR) must read and sign the informed consent; Parent or caregiver must agree to complete the required study visits and comply with the requirements of the study; Other protocol-specified inclusion criteria may apply. Exclusion Criteria: Menarcheal females; Previous otologic or otologic-related surgery within the past 30 days or ongoing complications; Existing perforation of the eardrum; Current acute otitis externa (AOE), malignant otitis externa (MOE) or other conditions which could interfere with evaluation of the study drug; Any systemic disease or disorder, complicating factor or structural abnormality that would negatively affect the conduct or outcome of the study; Use of prohibited medications or inadequate washout of any medication including systemic and topical antibiotics, steroids and/or analgesics; Weighs less than 8 kg; Other protocol-specified exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EXE844<br>EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion | Drug: EXE844 Sterile Otic Suspension, 0.3%<br> <br> Procedure: Tympanostomy Tube Insertion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Analyte Plasma Concentration (Cmax) | Based on serum samples collected at pre-determined nominal time points, dependent on observed concentrations. EXE844 (AL-60371) concentration values below the lower limit of quantification (<0.05 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. Similarly for EXE844 glucuronide metabolite (AL-91591), concentration values below the lower limit of quantification (<0.5 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. | Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose | 
| Time to Reach Maximum Concentration (Tmax) | Based on serum samples collected at pre-determined nominal time points, dependent on observed concentrations. EXE844 (AL-60371) concentration values below the lower limit of quantification (<0.05 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. Similarly for EXE844 glucuronide metabolite (AL-91591), concentration values below the lower limit of quantification (<0.5 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. | Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose | 
| Area Under the Plasma Concentration-time Curve to the Last Quantifiable Sampling Time Point (AUC0-last) | Based on serum samples collected at pre-determined nominal time points, dependent on observed concentrations. EXE844 (AL-60371) concentration values below the lower limit of quantification (<0.05 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. Similarly for EXE844 glucuronide metabolite (AL-91591), concentration values below the lower limit of quantification (<0.5 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. | Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose | 
| Area Under the Concentration-time Curve From 0 to Infinity (AUC0-inf) | Based on serum samples collected at pre-determined nominal time points, dependent on observed concentrations. EXE844 (AL-60371) concentration values below the lower limit of quantification (<0.05 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. Similarly for EXE844 glucuronide metabolite (AL-91591), concentration values below the lower limit of quantification (<0.5 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. | Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose | 
| Time to Last Measurable Concentration (Tlast) | Based on serum samples collected at pre-determined nominal time points, dependent on observed concentrations. EXE844 (AL-60371) concentration values below the lower limit of quantification (<0.05 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. Similarly for EXE844 glucuronide metabolite (AL-91591), concentration values below the lower limit of quantification (<0.5 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. | Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose | 
| Terminal Elimination Half-life (T1/2) | Based on serum samples collected at pre-determined nominal time points, dependent on observed concentrations. EXE844 (AL-60371) concentration values below the lower limit of quantification (<0.05 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. Similarly for EXE844 glucuronide metabolite (AL-91591), concentration values below the lower limit of quantification (<0.5 ng/mL) were replaced by one-half the lower limit of quantification in the calculation of the summary statistics. | Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose |