Trial Outcomes & Findings for Safety and Efficacy of EXE844 Otic Suspension in Otitis Media at Time of Tympanostomy Tube Insertion (OMTT) (NCT NCT02432105)

NCT ID: NCT02432105

Last Updated: 2018-07-02

Results Overview

A sustained clinical cure was attained if otorrhea was absent in the study ear at Day 8 (EOT) per the Investigator assessment and continued to be absent through the end of the study. Participants were considered a treatment failure if, at any time during the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 470 participants
• Primary outcome timeframe: Day 8
• Results posted on: 2018-07-02

Participant Flow

Participants were recruited from 18 study centers located in the US and 2 study centers located in Canada.

Of the 470 enrolled, 85 participants were exited as screen failures prior to randomization. This reporting group includes all randomized participants (385).

Participant milestones

Measure	EXE844 7 Days EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops, twice daily (BID) in each ear for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 3 days after Tympanostomy Tube Insertion	Tubes Only Bilateral myringotomy and tympanostomy tube insertion
Overall Study STARTED	164	110	111
Overall Study COMPLETED	162	108	108
Overall Study NOT COMPLETED	2	2	3

Reasons for withdrawal

Measure	EXE844 7 Days EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops, twice daily (BID) in each ear for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 3 days after Tympanostomy Tube Insertion	Tubes Only Bilateral myringotomy and tympanostomy tube insertion
Overall Study Lost to Follow-up	1	1	0
Overall Study Withdrawal by Subject	1	0	1
Overall Study Culture positive for yeast	0	1	0
Overall Study Randomized in error	0	0	2

Baseline Characteristics

Safety and Efficacy of EXE844 Otic Suspension in Otitis Media at Time of Tympanostomy Tube Insertion (OMTT)

Baseline characteristics by cohort

Measure	EXE844 7 Days n=164 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days n=110 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 3 days after Tympanostomy Tube Insertion	Tubes Only n=111 Participants Bilateral myringotomy and tympanostomy tube insertion	Total n=385 Participants Total of all reporting groups
Age, Continuous	2.2 years STANDARD_DEVIATION 1.82 • n=5 Participants	2.1 years STANDARD_DEVIATION 1.59 • n=7 Participants	2.2 years STANDARD_DEVIATION 1.92 • n=5 Participants	2.2 years STANDARD_DEVIATION 1.78 • n=4 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	45 Participants n=7 Participants	46 Participants n=5 Participants	147 Participants n=4 Participants
Sex: Female, Male Male	108 Participants n=5 Participants	65 Participants n=7 Participants	65 Participants n=5 Participants	238 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 8

Population: ITT analysis set

A sustained clinical cure was attained if otorrhea was absent in the study ear at Day 8 (EOT) per the Investigator assessment and continued to be absent through the end of the study. Participants were considered a treatment failure if, at any time during the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward).

Outcome measures

Measure	EXE844 7 Days n=164 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days n=110 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 3 days after Tympanostomy Tube Insertion	Tubes Only n=111 Participants Bilateral myringotomy and tympanostomy tube insertion
Percentage of Subjects With Sustained Clinical Cure at Day 8	76.2 percentage of participants	71.8 percentage of participants	56.8 percentage of participants

SECONDARY outcome

Timeframe: Day 14

Population: This analysis population includes all ITT subjects who were culture-positive at Day 1 in at least 1 ear (Microbiological Intent-to-Treat (MITT) analysis set).

Microbiological success was attained if all pretherapy bacteria were absent in the study ear for the Test-of-Cure (TOC) (Day 14) specimen. Participants were considered a treatment failure if, at any time during the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward).

Outcome measures

Measure	EXE844 7 Days n=96 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days n=60 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 3 days after Tympanostomy Tube Insertion	Tubes Only n=62 Participants Bilateral myringotomy and tympanostomy tube insertion
Percentage of Subjects With Microbiological Success at Day 14	74.0 percentage of participants	60.0 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Up to Day 14

Population: ITT analysis set

Time (in days) to the cessation of otorrhea in the enrolled ear(s) was calculated as the number of days from the day of surgery to the absence of otorrhea (ie, no discharge) as reported by the parent/caregiver via the BID diary. Participants were considered a treatment failure if, at any time during the course of the study, an alternative therapy was initiated to treat the postsurgical infection. All participants with missing or indeterminate outcomes were considered a failure (same as baseline observation carried forward).

Outcome measures

Measure	EXE844 7 Days n=164 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days n=110 Participants EXE844 Sterile Otic Suspension, 0.3%, ototopical, 4 drops BID in each ear for 3 days after Tympanostomy Tube Insertion	Tubes Only n=111 Participants Bilateral myringotomy and tympanostomy tube insertion
Time to Cessation of Otorrhea	2.5 days Interval 1.5 to 3.5	1.5 days Interval 1.0 to 2.5	8.0 days Interval 2.5 to 13.0

Adverse Events

Pretreatment

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

EXE844 7 Days

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

EXE844 3 Days

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Tubes Only

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pretreatment n=470 participants at risk All AEs reported prior to randomization	EXE844 7 Days n=164 participants at risk All participants treated with EXE844 Sterile Otic Suspension, 0.3% for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days n=110 participants at risk All participants treated with EXE844 Sterile Otic Suspension, 0.3% for 3 days after Tympanostomy Tube Insertion	Tubes Only n=111 participants at risk All participants treated with bilateral myringotomy and tympanostomy tube insertion only
Gastrointestinal disorders Intussusception	0.00% 0/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.00% 0/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.91% 1/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.00% 0/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.
Infections and infestations Viral rash	0.00% 0/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.61% 1/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.00% 0/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.00% 0/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.
Respiratory, thoracic and mediastinal disorders Asthma	0.21% 1/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.00% 0/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.00% 0/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	0.00% 0/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.

Other adverse events

Measure	Pretreatment n=470 participants at risk All AEs reported prior to randomization	EXE844 7 Days n=164 participants at risk All participants treated with EXE844 Sterile Otic Suspension, 0.3% for 7 days after Tympanostomy Tube Insertion	EXE844 3 Days n=110 participants at risk All participants treated with EXE844 Sterile Otic Suspension, 0.3% for 3 days after Tympanostomy Tube Insertion	Tubes Only n=111 participants at risk All participants treated with bilateral myringotomy and tympanostomy tube insertion only
Ear and labyrinth disorders Otorrhoea	0.00% 0/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	3.7% 6/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	5.5% 6/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	14.4% 16/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.
Ear and labyrinth disorders Ear pain	0.21% 1/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	1.2% 2/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	4.5% 5/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	5.4% 6/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.
Infections and infestations Upper respiratory tract infection	1.1% 5/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	3.0% 5/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	5.5% 6/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	7.2% 8/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.
General disorders Pyrexia	0.21% 1/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	9.8% 16/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	8.2% 9/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	12.6% 14/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.
Gastrointestinal disorders Vomiting	0.21% 1/470 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	1.2% 2/164 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	1.8% 2/110 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.	6.3% 7/111 • Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 19 days).This analysis population includes all participants who had tympanostomy tubes inserted and were randomized. AEs are reported as pre-treatment and treatment-emergent. An AE was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from participants and through observations by the Investigator as outlined in the study protocol.

Additional Information

Clinical Scientific Director, GCRA - Global Clinical Development

Alcon, A Novartis Division

Phone: 1-888-451-3937

Email: alcon.medinfo@alcon.com

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