Trial Outcomes & Findings for Comparative Efficacy and Safety of Ciprofloxacin 0.3% and Dexamethasone 0.1% in Acute Otitis Externa (NCT NCT02216071)

Last Updated: 2021-05-28

Results Overview

The primary efficacy endpoint was the clinical cure of AOE, defined as the proportion of subjects with a clinical AOE score of 0 at the TOC Visit. Subjects with AOE in both ears were considered to have achieved clinical cure of AOE if the clinical AOE score was 0 for both ears. The clinical AOE score was defined as the sum of scores for inflammation and edema (0=absent, 1=mild, 2=moderate, 3=severe) and tenderness and otorrhea (0=absent, 1=present).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

499 participants

Primary outcome timeframe

7 days after the completion of therapy; at Day 15 (+/- 1 day)

Results posted on

2021-05-28

Participant Flow

Participant milestones

Participant milestones
Measure	Ciprodex®, RLD Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	EXL CDOS EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Overall Study STARTED	254	245
Overall Study COMPLETED	239	233
Overall Study NOT COMPLETED	15	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Ciprodex®, RLD Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	EXL CDOS EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Overall Study Withdrawal by Subject	7	2
Overall Study Lost to Follow-up	3	3
Overall Study Protocol Violation	3	5
Overall Study Other	2	2

Baseline Characteristics

Comparative Efficacy and Safety of Ciprofloxacin 0.3% and Dexamethasone 0.1% in Acute Otitis Externa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ciprodex®, RLD n=254 Participants Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	EXL CDOS n=245 Participants EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	Total n=499 Participants Total of all reporting groups
Age, Continuous	33.3 years STANDARD_DEVIATION 24.50 • n=99 Participants	33.1 years STANDARD_DEVIATION 23.54 • n=107 Participants	33.2 years STANDARD_DEVIATION 24.01 • n=206 Participants
Sex: Female, Male Female	132 Participants n=99 Participants	131 Participants n=107 Participants	263 Participants n=206 Participants
Sex: Female, Male Male	122 Participants n=99 Participants	114 Participants n=107 Participants	236 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	81 Participants n=99 Participants	85 Participants n=107 Participants	166 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	173 Participants n=99 Participants	160 Participants n=107 Participants	333 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Asian	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) Black or African American	16 Participants n=99 Participants	26 Participants n=107 Participants	42 Participants n=206 Participants
Race (NIH/OMB) White	233 Participants n=99 Participants	210 Participants n=107 Participants	443 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Region of Enrollment Puerto Rico	18 participants n=99 Participants	15 participants n=107 Participants	33 participants n=206 Participants
Region of Enrollment United States	236 participants n=99 Participants	230 participants n=107 Participants	466 participants n=206 Participants

PRIMARY outcome

Timeframe: 7 days after the completion of therapy; at Day 15 (+/- 1 day)

Outcome measures

Outcome measures
Measure	EXL CDOS n=245 Participants EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	Ciprodex®, RLD n=254 Participants Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Number of Participants With Clinical Cure of AOE	191 Participants	190 Participants

SECONDARY outcome

Timeframe: 7 days after the completion of therapy; at Day 15 (+/- 1 day)

Population: The number of participants analyzed represents Bacteria-Positive cohort of subjects

The secondary efficacy endpoint was the microbiological cure of AOE, defined as the proportion of subjects with microbiological cure at the TOC Visit. Subjects with AOE in both ears were considered to have achieved microbiological cure if microbiological cure was achieved in both ears.

Outcome measures

Outcome measures
Measure	EXL CDOS n=149 Participants EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	Ciprodex®, RLD n=160 Participants Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Number of Participants With Microbiological Cure (MC)	117 Participants	115 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Each monitoring visit through 15 +/- 1 days

Population: 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.

Safety outcomes evaluated * AEs

Outcome measures

Outcome measures
Measure	EXL CDOS n=252 Participants EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	Ciprodex®, RLD n=247 Participants Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Number of Participants With Adverse Events	67 Participants	60 Participants

Adverse Events

Ciprodex®, RLD

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

EXL CDOS

Serious events: 1 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ciprodex®, RLD n=247 participants at risk Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	EXL CDOS n=252 participants at risk EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Musculoskeletal and connective tissue disorders TMJ Syndrome	0.00% 0/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.40% 1/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.

Other adverse events

Other adverse events
Measure	Ciprodex®, RLD n=247 participants at risk Ciprodex®, Otic Suspension, Twice daily for 7 days Ciprodex®: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days	EXL CDOS n=252 participants at risk EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension, Otic Suspension, Twice daily for 7 days EXL CDOS (Ciprofloxacin 0.3% and Dexamethasone 0.1%) Sterile Otic Suspension: Treatment of acute otitis externa (AOE) when administered twice daily for 7 days
Ear and labyrinth disorders Ear and labyrinth disorder	7.3% 18/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	6.0% 15/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Eye disorders Photophobia	0.00% 0/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.40% 1/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Gastrointestinal disorders Gastrointestinal	0.40% 1/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.79% 2/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
General disorders General disorder and administration site conditions	1.2% 3/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.40% 1/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Infections and infestations Infections and Infestations	5.3% 13/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	7.1% 18/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	2.4% 6/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	1.2% 3/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Investigations Heart rate increased	0.00% 0/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.40% 1/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.40% 1/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.81% 2/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.79% 2/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Nervous system disorders Nercous system disorders	2.0% 5/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	2.0% 5/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracid and mediastinal disorders	1.6% 4/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	1.2% 3/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	0.40% 1/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	1.6% 4/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.
Social circumstances Menarche	0.00% 0/247 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.	0.40% 1/252 499 subjects were randomized as the ITT population, 245 in the EXL CDOS arm \& 254 in the RLD arm. All were included in the safety population, but randomization was modified for 36 subjects in the EXL CDOS arm and 43 subjects in the RLD arm to account for available supply of study drug, making 252 subjects in the EXL CDOS arm \& 247 in the RLD arm.

Additional Information

Aruna Koganti, VP Clinical Programs

Exela Pharma Sciences

Phone: 828-758-5474

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place