Trial Outcomes & Findings for OTO-201 for the Treatment of Middle Ear Effusion in Pediatric Subjects Requiring Tympanostomy Tube Placement (NCT NCT01949142)

NCT ID: NCT01949142

Last Updated: 2016-06-15

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: 2016-06-15

Participant Flow

Participants were recruited from 29 centers, 25 in the United States and 4 from Canada.

The reporting group includes all randomized participants (n=266)

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	179	87
Overall Study COMPLETED	176	86
Overall Study NOT COMPLETED	3	1

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 Withdrawal of consent	1	0
Overall Study Lost to Follow-up	1	1
Overall Study Parent changed their mind	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	Total n=266 Participants Total of all reporting groups	OTO-201 n=179 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.
Age, Continuous	2.416 years STANDARD_DEVIATION 2.0826 • n=5 Participants	2.392 years STANDARD_DEVIATION 2.0710 • n=5 Participants	2.463 years STANDARD_DEVIATION 2.1176 • n=7 Participants
Sex: Female, Male Female	106 Participants n=5 Participants	75 Participants n=5 Participants	31 Participants n=7 Participants
Sex: Female, Male Male	160 Participants n=5 Participants	104 Participants n=5 Participants	56 Participants n=7 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=179 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.
Percentage of Participants Who Were Treatment Failures	24.6 percentage of treatment failures	44.8 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, vital sign measurements, and physical examinations.

Outcome measures

Measure	OTO-201 n=179 Participants OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham n=86 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-right ear	0.6 percentage of ears	0.0 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry, and Tympanometry Audiometry Patent tubes @ day 29-left ear	98.3 percentage of ears	94.1 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry, and Tympanometry Otoscopic abnormal exams @ day 29-left ear	1.1 percentage of ears	2.4 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	89.2 percentage of ears	84.1 percentage of ears
Evaluation of Adverse Events, Otoscopic Exams, Audiometry, and Tympanometry Tympanometry Category of B (large)day 29-right ear	91.0 percentage of ears	88.9 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.

Outcome measures

Measure	OTO-201 n=41 Participants OTO-201: Single, intratympanic injection: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham n=22 Participants Sham: Simulated single, intratympanic injection: One sham injection into each ear during surgery.
Microbiological Response	81 percentage of Microbiological response	41 percentage of Microbiological response

Adverse Events

OTO-201 Single, Intratympanic Injection

Serious events: 3 serious events

Other events: 64 other events

Deaths: 0 deaths

Sham-Simulated Single, Intratympanic Injection

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	OTO-201 Single, Intratympanic Injection n=179 participants at risk OTO-201: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham-Simulated Single, Intratympanic Injection n=86 participants at risk Sham: One sham injection into each ear during surgery.
Infections and infestations Bronchiolitis	1.1% 2/179 • Number of events 2 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	0.00% 0/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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 Gastroenteritis	0.56% 1/179 • Number of events 1 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	0.00% 0/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.

Other adverse events

Measure	OTO-201 Single, Intratympanic Injection n=179 participants at risk OTO-201: One injection of 6 mg OTO-201 (ciprofloxacin in poloxamer 407) into each ear during surgery.	Sham-Simulated Single, Intratympanic Injection n=86 participants at risk Sham: One sham injection into each ear during surgery.
General disorders Irritability	5.6% 10/179 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	2.3% 2/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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 Nasopharyngitis	6.7% 12/179 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	4.7% 4/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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	6.1% 11/179 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	3.5% 3/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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	6.1% 11/179 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	3.5% 3/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.
General disorders Pyrexia	8.4% 15/179 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	10.5% 9/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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	2.8% 5/179 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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.	8.1% 7/86 • Up to 6 weeks for each subject with total study time of 7 months. All AEs 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