Trial Outcomes & Findings for OTO-201 for the Treatment of Middle Ear Effusion in Pediatric Subjects Requiring Tympanostomy Tube Placement (NCT NCT01949155)

NCT ID: NCT01949155

Last Updated: 2016-11-11

Results Overview

Cumulative proportion of treatment failures: The efficacy endpoint for both trials was the cumulative proportion of study treatment failures through Day 15, defined as the occurrence of any of the following events: otorrhea as determined by a blinded assessor on or after 3 days post-surgery, otic or systemic antibacterial drug use for any reason any time post-surgery, as well as patients who missed visits or were lost-to-follow-up.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 266 participants
• Primary outcome timeframe: Day 15 - 2 weeks after dosing
• Results posted on: 2016-11-11

Participant Flow

Participants were recruited from 19 centers, 18 in the United States and 1 in Canada

Reporting group = all randomized participants (n=266). Safety analysis set = all subjects who receive study drug or sham and analyzed according to what they received. Full analysis set = all randomized subjects and analyzed according to randomized treatment regardless of the actual treatment received.

Participant milestones

Measure	OTO-201 OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.
Overall Study STARTED	178	88
Overall Study COMPLETED	176	88
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	OTO-201 OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.
Overall Study Lost to Follow-up	1	0
Overall Study Protocol Violation	1	0

Baseline Characteristics

OTO-201 for the Treatment of Middle Ear Effusion in Pediatric Subjects Requiring Tympanostomy Tube Placement

Baseline characteristics by cohort

Measure	OTO-201 n=178 Participants OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham n=88 Participants Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.	Total n=266 Participants Total of all reporting groups
Age, Categorical <=18 years	178 Participants n=93 Participants	88 Participants n=4 Participants	266 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	2.279 years STANDARD_DEVIATION 1.9010 • n=93 Participants	2.863 years STANDARD_DEVIATION 2.5942 • n=4 Participants	2.472 years STANDARD_DEVIATION 2.1677 • n=27 Participants
Sex: Female, Male Female	82 Participants n=93 Participants	40 Participants n=4 Participants	122 Participants n=27 Participants
Sex: Female, Male Male	96 Participants n=93 Participants	48 Participants n=4 Participants	144 Participants n=27 Participants

PRIMARY outcome

Timeframe: Day 15 - 2 weeks after dosing

Population: Full Analysis Set

Cumulative proportion of treatment failures:

The efficacy endpoint for both trials was the cumulative proportion of study treatment failures through Day 15, defined as the occurrence of any of the following events: otorrhea as determined by a blinded assessor on or after 3 days post-surgery, otic or systemic antibacterial drug use for any reason any time post-surgery, as well as patients who missed visits or were lost-to-follow-up.

Outcome measures

Measure	OTO-201 n=178 Participants OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham n=88 Participants Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.
Percentage of Participants Who Were Treatment Failures.	21.3 percentage of treatment failures	45.5 percentage of treatment failures

SECONDARY outcome

Timeframe: Up to one month

Population: Safety Analysis Set (number of ears is equivalent to number of participants)

Safety variables included the frequency of adverse events (AEs) and results from otoscopic examinations, tympanometry, audiometry measurements.

Outcome measures

Measure	OTO-201 n=178 Participants OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham n=87 Participants Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.
Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry Otoscopic abnormal exams @ day 29-left ear	1.7 percentage of ears	2.4 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry Otoscopic abnormal exams @ day 29-right ear	1.7 percentage of ears	3.5 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry Audiometry Patent tubes @ day 29 left ear	96.0 percentage of ears	100 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry Audiometry Patent tubes @ day 29 right ear	96.0 percentage of ears	96.5 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry Tympanometry Category of B (large) day 29 left ear	87.9 percentage of ears	87.1 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry and Tympanometry Tympanometry Category of B (large)day 29 right ear	88.2 percentage of ears	84.5 percentage of ears

SECONDARY outcome

Timeframe: Day 15 - 2 weeks after dosing

Population: Microbiologically Evaluable Set

Subjects whose samples tested positive for bacteria in either or both ears at baseline with documented eradication or presumed eradication post-baseline.

Outcome measures

Measure	OTO-201 n=29 Participants OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham n=27 Participants Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.
Microbiological Response	83 percentage of Microbiological response	48 percentage of Microbiological response

Adverse Events

OTO-201

Serious events: 0 serious events

Other events: 75 other events

Deaths: 0 deaths

Sham

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	OTO-201 n=178 participants at risk OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham n=87 participants at risk Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.
General disorders Pyrexia	14.0% 25/178 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.	12.6% 11/87 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.
Injury, poisoning and procedural complications Procedural pain	7.3% 13/178 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.	12.6% 11/87 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.
Gastrointestinal disorders Teething	7.3% 13/178 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.	5.7% 5/87 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 12/178 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.	4.6% 4/87 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.
Infections and infestations Upper respiratory tract infection	6.7% 12/178 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.	10.3% 9/87 • Up to 6 weeks for each subject with total study time of 7 months. All AE's reported or observed after the informed consent had been signed and during or after dosing with the study drug were recorded on the AE page of the eCRF for all randomized subjects.

Additional Information

Medical Information Call Center

Otonomy, Inc.

Phone: 1-800-826-6411

Email: medinfo@otonomy.com

Results disclosure agreements

• Principal investigator is a sponsor employee From the Protocol; 14.11. Use of Information and Publication. All information concerning OTO-201...remains the sole property of Otonomy. Any publication or other public presentation of results from this study requires prior review and written approval of Otonomy. Draft abstracts, manuscripts, and materials for presentation at scientific meetings should be provided to the sponsor at least 30 working days prior to abstract or other relevant submission deadlines.
• Publication restrictions are in place

Restriction type: OTHER