Trial Outcomes & Findings for Pediatric Pharmacokinetic (PK) Study of EXE844 Otic Suspension in Otitis Media at the Time of Tympanostomy Tube Insertion (OMTT) (NCT NCT02539654)

NCT ID: NCT02539654

Last Updated: 2018-08-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose

Results posted on

2018-08-07

Participant Flow

Participants were recruited from 2 investigational sites located in the US.

All 14 enrolled participants were treated. This reporting group includes all enrolled participants (14).

Participant milestones

Participant milestones
Measure
EXE844
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Overall Study
STARTED
14
Overall Study
COMPLETED
14
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
EXE844
n=14 Participants
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Age, Continuous
3.4 years
STANDARD_DEVIATION 2.78 • n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose

Population: PK analysis set, with at least 1 post-dose quantifiable plasma concentration for each individual analyte \[EXE844 (AL-60371) and EXE844 glucuronide metabolite (AL-91591)\]

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.

Outcome measures

Outcome measures
Measure
EXE844
n=14 Participants
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Maximum Analyte Plasma Concentration (Cmax)
AL-60371
2.44 ng/mL
Standard Deviation 2.411
Maximum Analyte Plasma Concentration (Cmax)
AL-91591
1.61 ng/mL
Standard Deviation 1.141

PRIMARY outcome

Timeframe: Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose

Population: PK analysis set, with at least 1 post-dose quantifiable plasma concentration for each individual analyte \[EXE844 (AL-60371) and EXE844 glucuronide metabolite (AL-91591)\]

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.

Outcome measures

Outcome measures
Measure
EXE844
n=14 Participants
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Time to Reach Maximum Concentration (Tmax)
AL-60371
0.59 hours
Interval 0.48 to 2.1
Time to Reach Maximum Concentration (Tmax)
AL-91591
1.00 hours
Interval 0.55 to 2.17

PRIMARY outcome

Timeframe: Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose

Population: PK analysis set, with at least 1 post-dose quantifiable plasma concentration for each individual analyte \[EXE844 (AL-60371) and EXE844 glucuronide metabolite (AL-91591)\]

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.

Outcome measures

Outcome measures
Measure
EXE844
n=9 Participants
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Area Under the Plasma Concentration-time Curve to the Last Quantifiable Sampling Time Point (AUC0-last)
AL-60371
8.66 ng*h/mL
Standard Deviation 6.406
Area Under the Plasma Concentration-time Curve to the Last Quantifiable Sampling Time Point (AUC0-last)
AL-91591
3.94 ng*h/mL
Standard Deviation 4.136

PRIMARY outcome

Timeframe: Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose

Population: PK analysis set, with at least 1 post-dose quantifiable plasma concentration for each individual analyte \[EXE844 (AL-60371) and EXE844 glucuronide metabolite (AL-91591)\]

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.

Outcome measures

Outcome measures
Measure
EXE844
n=8 Participants
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-inf)
AL-60371
10.60 ng*h/mL
Standard Deviation 7.764
Area Under the Concentration-time Curve From 0 to Infinity (AUC0-inf)
AL-91591
19.90 ng*h/mL
Standard Deviation NA
Unable to compute estimate

PRIMARY outcome

Timeframe: Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose

Population: PK analysis set, with at least 1 post-dose quantifiable plasma concentration for each individual analyte \[EXE844 (AL-60371) and EXE844 glucuronide metabolite (AL-91591)\]

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.

Outcome measures

Outcome measures
Measure
EXE844
n=11 Participants
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Time to Last Measurable Concentration (Tlast)
AL-60371
5.90 hours
Interval 1.08 to 6.1
Time to Last Measurable Concentration (Tlast)
AL-91591
2.17 hours
Interval 1.0 to 5.95

PRIMARY outcome

Timeframe: Day 1, pre-dose 0 hour (up to 30 minutes prior to dose), 0.5, 1, 2, 4, 6 hours post-dose

Population: PK analysis set, with at least 1 post-dose quantifiable plasma concentration for each individual analyte \[EXE844 (AL-60371) and EXE844 glucuronide metabolite (AL-91591)\]

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.

Outcome measures

Outcome measures
Measure
EXE844
n=8 Participants
EXE844 Sterile Otic Suspension, 0.3%, single ototopical dose (4 drops) in each ear following tympanostomy tube insertion
Terminal Elimination Half-life (T1/2)
AL-91591
4.42 hours
Standard Deviation NA
Unable to compute estimate
Terminal Elimination Half-life (T1/2)
AL-60371
2.05 hours
Standard Deviation 0.821

Adverse Events

Pre-treatment

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

EXE844

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Clinical Scientific Director, GCRA

Alcon, A Novartis Division

Phone: 1-888-451-3937

Results disclosure agreements

  • Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
  • Publication restrictions are in place

Restriction type: OTHER