ELLIOTT: Study of Safety and Efficacy for the Eustachian Tube Balloon Catheter

• Sponsor: Acclarent (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02087150
• Collaborator: (none)
• Enrollment: 323
• Locations: 21
• Arms: 2
• Actual Duration (Months): 35.4
• Patients Per Site: 15.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The objective of this study is to determine whether Eustachian tube dilation in conjunction with medical management or medical management alone is effective for treating Eustachian tube dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Eustachian Tube Dysfunction	Device: Acclarent Eustachian Tube Balloon Catheter (ETBC)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 323 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Clinical Study of Safety and Efficacy for the Eustachian Tube Balloon Catheter (ELLIOTT)
• Actual Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Jan 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Medical management (MM) Medical management will consist of 6 weeks of daily intranasal steroid (triamcinolone acetonide)
Experimental: Eustachian tube balloon catheter (ETBC) plus MM Eustachian tube dilation with the ETBC plus medical management	Device: Acclarent Eustachian Tube Balloon Catheter (ETBC)

Outcome Measures

Primary Outcome Measures

1. Primary Efficacy Analysis: Number of Randomized Subjects With Tympanogram Normalization at 6 Weeks [6 Week Follow-Up Visit]

   The primary efficacy analysis compares randomized subjects with tympanogram normalization (Types B or C normalized to Type A) in all indicated ears at 6 weeks in the investigational arm versus the control arm. Per protocol, tympanogram types are defined as follows: Type A: Peak compliance occurs between +50 and -100 daPa, with minimum peak height of 0.2ml. Indicates NORMAL middle ear function Type B: No sharp peak and a rounded line. Indicates ABNORMAL middle ear function Type C: Peak compliance occurs beyond -100 daPa. Indicates ABNORMAL middle ear function

Secondary Outcome Measures

1. Secondary Efficacy Endpoint: Number of Randomized Subjects With MID Improvement From Baseline of 0.5 Points or More at 6 Weeks [6 Week Follow-Up Visit]

   The secondary efficacy endpoint will consist of comparison of subjects achieving at least a minimally important difference (MID) level improvement of 0.5 points on the ETDQ-7 at 6 weeks post-treatment in the investigational arm versus the proportion of subjects achieving at least an MID level improvement on the ETDQ-7 at 6 weeks post-randomization in the control arm The ETDQ-7 is a seven-item ETD specific validated quality of life survey. A mean item score of greater or equal to 2.1 indicates the presence of ETD.

Other Outcome Measures

1. Exploratory Endpoint: Number of Randomized Subjects With Normalized Tympanometry at 12.24,52 Weeks [12, 24, 52 Week Follow-Up]

   Evaluation of subjects experiencing normalization of tympanometry at 12 weeks, 24 weeks, and 52 weeks post-treatment in the investigational arm and evaluation of subjects experiencing normalization of tympanometry at 12 weeks, 24 weeks, and 52 weeks post-randomization in the control arm. As MM subjects were allowed to receive a crossover procedure after their 6-week follow-up visit, there is a limited number of MM subjects who completed the 12/24/52 visits.

2. Exploratory Endpoint: Number of Randomized Subjects With ETDQ-7 Improvement at 12, 24, 52 Weeks [12,24,52 Week Follow-Up Visit]

   Evaluation of subjects achieving at least a MID level improvement of 0.5 points at 12 weeks, 24 weeks, and 52 weeks post-treatment in the investigational arm and evaluation of subjects achieving at least a MID level improvement at 12 weeks, 24 weeks, and 52 weeks post-randomization in the control arm. As MM subjects were allowed to receive a crossover procedure after their 6-week follow-up visit, there is a limited number of MM subjects who completed the 12/24/52 visits.

3. Exploratory Endpoint: WPAI at 6,12,24,52 Weeks [6,12,24,52 Week Follow-Up]

   Evaluation of subjects' work and activity impairment before and after treatment in both the investigational arm and the control arm. The Work Productivity and Activity Impairment (WPAI) questionnaire is a 6-question patient-reported general health assessment of productivity and activity impairment. WPAI results are expressed as the percentage of impairment from 0 to 100 where higher numbers indicate greater impairment or less productivity. Due to an error in the WPAI electronic data collection form, 2 questions were not visible to many subjects resulting in a significant amount of missing data for all scores except non-work activity impairment. Therefore, only the non-work activity impairment results are presented. As MM subjects were allowed to receive a crossover procedure after their 6-week follow-up visit, there is a limited number of MM subjects who completed the 12/24/52 visits.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult male or female aged 22 years and older

• Persistent Eustachian tube dysfunction

• Failure of medical management

• Positive diagnosis of ETD

• Absence of internal carotid artery (ICA) dehiscence

• Able to read and understand English

Exclusion Criteria:

• Females who are pregnant or lactating

• Anatomy that requires an adjunctive surgical procedure

• Concomitant nasal or sinus procedures planned on the same day as surgical procedure

• Concomitant ear procedures planned on the same day as surgical procedure

• History of major surgery of the head or neck within four (4) months prior to surgery

• History of patulous ET

• History of fluctuating sensorineural hearing loss

• Active acute otitis media

• Tympanic membrane perforation

• Tympanosclerosis

• Acute upper respiratory infection

• Temporomandibular joint disorder

• Cleft palate

• Craniofacial syndrome

• Cystic fibrosis

• Ciliary dysmotility syndrome

• Systemic mucosal or immunodeficiency disease

• Intolerance of medication for ETD

• Prior intervention of Eustachian tube

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Ear Institute	East Palo Alto	California	United States	94303
2	George Washington Medical Faculty Associates, ENT Center	Washington	District of Columbia	United States	20006
3	ENT of South Florida	Boca Raton	Florida	United States	33487
4	ENT of South Florida	Boynton Beach	Florida	United States	33437
5	Florida Ear & Sinus Center	Sarasota	Florida	United States	34239
6	ENT of Georgia	Atlanta	Georgia	United States	30308
7	Piedmont Ear, Nose & Throat &Related Allergy	Atlanta	Georgia	United States	30309
8	Witham Health Services	Lebanon	Indiana	United States	46052
9	Red River Sinus Center	Alexandria	Louisiana	United States	71303
10	Our Lady of the Lake Hospital	Baton Rouge	Louisiana	United States	70808
11	Children's Hospital	Boston	Massachusetts	United States	02115
12	Health Partners Specialty Center	Saint Paul	Minnesota	United States	55130
13	The Sinus Center of the South	Ocean Springs	Mississippi	United States	39564
14	Vijay Anand, LLC	New York	New York	United States	10021
15	Ear, Nose, Throat and Allergy Associates, LLP	Port Jefferson	New York	United States	11777
16	Ear, Nose, Throat and Allergy Associates, LLP	White Plains	New York	United States	10601
17	Charlotte Eye, Ear, Nose &Throat Associates	Charlotte	North Carolina	United States	28210
18	Carolina Ear and Hearing Clinic	Raleigh	North Carolina	United States	27609
19	Texas Healthcare, PLLC	Fort Worth	Texas	United States	76104
20	Ear Medical Group	San Antonio	Texas	United States	78240
21	Meriter Monona	Monona	Wisconsin	United States	53716

Sponsors and Collaborators

• Acclarent

Investigators

• Principal Investigator: Dennis Poe, MD, PhD, Boston Children's Hospital
• Principal Investigator: Vijay Anand, MD, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acclarent
• ClinicalTrials.gov Identifier: NCT02087150
• Other Study ID Numbers: CPR005029
• First Posted: Mar 14, 2014
• Last Update Posted: Jan 8, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Study Results

Participant Flow

Arm/Group Title	Lead-In	Randomized ETBC	Randomized MM
Arm/Group Description	Subjects enrolled in Lead-In Group	Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)	Subjects enrolled and randomized to treatment with medical management (MM) only. Subjects randomized to the MM arm were allowed the option to cross-over to have a procedure with the ETBC after completion of the 6 week follow-up visit. Cross-over subject were followed to 12 weeks post-procedure only. Thereafter, they were exited from the study and not required to undergo the 24 week and 52 week follow-up visits
Period Title: Overall Study
STARTED	81	162	80
Had a Lead-in or Randomized ETBC Proc	80	149	0
Received a Crossover MM ETBC Procedure	0	0	70
COMPLETED	71	128	69
NOT COMPLETED	10	34	11

Baseline Characteristics

Arm/Group Title	Lead-In	Randomized ETBC	Randomized MM	Total
Arm/Group Description	Subjects enrolled in Lead-In Group	Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)	Subjects enrolled and randomized to treatment with medical management (MM) only. Subjects randomized to the MM arm were allowed the option to cross-over to have a procedure with the ETBC after completion of the 6 week follow-up visit. Cross-over subject were followed to 12 weeks post-procedure only. Thereafter, they were exited from the study and not required to undergo the 24 week and 52 week follow-up visits	Total of all reporting groups
Overall Participants	81	162	80	323
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.7 (14.1)	55.6 (14.3)	57.7 (13.4)	55.6 (14.1)
Sex: Female, Male (Count of Participants)
Female	30 37%	77 47.5%	48 60%	155 48%
Male	51 63%	85 52.5%	32 40%	168 52%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.2%	9 5.6%	2 2.5%	12 3.7%
Not Hispanic or Latino	80 98.8%	153 94.4%	78 97.5%	311 96.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 1.2%	0 0%	1 1.3%	2 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 3.7%	12 7.4%	8 10%	23 7.1%
White	77 95.1%	147 90.7%	67 83.8%	291 90.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	3 1.9%	4 5%	7 2.2%

Outcome Measures

1. Primary Outcome

Title	Primary Efficacy Analysis: Number of Randomized Subjects With Tympanogram Normalization at 6 Weeks
Description	The primary efficacy analysis compares randomized subjects with tympanogram normalization (Types B or C normalized to Type A) in all indicated ears at 6 weeks in the investigational arm versus the control arm. Per protocol, tympanogram types are defined as follows: Type A: Peak compliance occurs between +50 and -100 daPa, with minimum peak height of 0.2ml. Indicates NORMAL middle ear function Type B: No sharp peak and a rounded line. Indicates ABNORMAL middle ear function Type C: Peak compliance occurs beyond -100 daPa. Indicates ABNORMAL middle ear function
Time Frame	6 Week Follow-Up Visit

Outcome Measure Data

Analysis Population Description

Primary Analysis Cohort (PAC): The PAC is defined as all randomized subjects who receive a study treatment for which they are randomized and have completed their primary analysis visits (i.e. completer analysis with baseline and 6 week tympanogram).

Arm/Group Title	Randomized ETBC	Randomized MM
Arm/Group Description	Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)	Subjects enrolled and randomized to treatment with medical management (MM) only. Subjects randomized to the MM arm were allowed the option to cross-over to have a procedure with the ETBC after completion of the 6 week follow-up visit. Cross-over subject were followed to 12 weeks post-procedure only. Thereafter, they were exited from the study and not required to undergo the 24 week and 52 week follow-up visits
Measure Participants	143	72
Participants with normalized tympanograms	73 90.1%	10 6.2%

2. Secondary Outcome

Title	Secondary Efficacy Endpoint: Number of Randomized Subjects With MID Improvement From Baseline of 0.5 Points or More at 6 Weeks
Description	The secondary efficacy endpoint will consist of comparison of subjects achieving at least a minimally important difference (MID) level improvement of 0.5 points on the ETDQ-7 at 6 weeks post-treatment in the investigational arm versus the proportion of subjects achieving at least an MID level improvement on the ETDQ-7 at 6 weeks post-randomization in the control arm The ETDQ-7 is a seven-item ETD specific validated quality of life survey. A mean item score of greater or equal to 2.1 indicates the presence of ETD.
Time Frame	6 Week Follow-Up Visit

Outcome Measure Data

Analysis Population Description

Primary Analysis Cohort (PAC): The PAC is defined as all randomized subjects who receive a study treatment for which they are randomized and have completed their primary analysis visits (i.e. completer analysis with baseline and 6 week tympanogram).

Arm/Group Title	Randomized ETBC	Randomized MM
Arm/Group Description	Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)	Subjects enrolled and randomized to treatment with medical management (MM) only. Subjects randomized to the MM arm were allowed the option to cross-over to have a procedure with the ETBC after completion of the 6 week follow-up visit. Cross-over subject were followed to 12 weeks post-procedure only. Thereafter, they were exited from the study and not required to undergo the 24 week and 52 week follow-up visits
Measure Participants	143	72
Participants with MID improvement of 0.5 or more	128 158%	32 19.8%

3. Other Pre-specified Outcome

Title	Exploratory Endpoint: Number of Randomized Subjects With Normalized Tympanometry at 12.24,52 Weeks
Description	Evaluation of subjects experiencing normalization of tympanometry at 12 weeks, 24 weeks, and 52 weeks post-treatment in the investigational arm and evaluation of subjects experiencing normalization of tympanometry at 12 weeks, 24 weeks, and 52 weeks post-randomization in the control arm. As MM subjects were allowed to receive a crossover procedure after their 6-week follow-up visit, there is a limited number of MM subjects who completed the 12/24/52 visits.
Time Frame	12, 24, 52 Week Follow-Up

Outcome Measure Data

Analysis Population Description

Per-Protocol Cohort: All randomized subjects expect those who: • Did not complete a baseline or respective follow-up assessment for the time point under analysis • Did not receive the treatment for which they were randomized • Had any major protocol deviation(s)

Arm/Group Title	Randomized ETBC	Randomized MM
Arm/Group Description	Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)	Subjects enrolled and randomized to treatment with medical management (MM) only. Subjects randomized to the MM arm were allowed the option to cross-over to have a procedure with the ETBC after completion of the 6 week follow-up visit. Cross-over subject were followed to 12 weeks post-procedure only. Thereafter, they were exited from the study and not required to undergo the 24 week and 52 week follow-up visits
Measure Participants	149	80
12 Week Visit	64 79%	7 4.3%
24 Week Visit	78 96.3%	5 3.1%
52 Week Visit	71 87.7%	2 1.2%

4. Other Pre-specified Outcome

Title	Exploratory Endpoint: Number of Randomized Subjects With ETDQ-7 Improvement at 12, 24, 52 Weeks
Description	Evaluation of subjects achieving at least a MID level improvement of 0.5 points at 12 weeks, 24 weeks, and 52 weeks post-treatment in the investigational arm and evaluation of subjects achieving at least a MID level improvement at 12 weeks, 24 weeks, and 52 weeks post-randomization in the control arm. As MM subjects were allowed to receive a crossover procedure after their 6-week follow-up visit, there is a limited number of MM subjects who completed the 12/24/52 visits.
Time Frame	12,24,52 Week Follow-Up Visit

Outcome Measure Data

Analysis Population Description

Per-Protocol Cohort: All randomized subjects expect those who: • Did not complete a baseline or respective follow-up assessment for the time point under analysis • Did not receive the treatment for which they were randomized • Had any major protocol deviation(s)

Arm/Group Title	Randomized ETBC	Randomized MM
Arm/Group Description	Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)	Subjects enrolled and randomized to treatment with medical management (MM) only. Subjects randomized to the MM arm were allowed the option to cross-over to have a procedure with the ETBC after completion of the 6 week follow-up visit. Cross-over subject were followed to 12 weeks post-procedure only. Thereafter, they were exited from the study and not required to undergo the 24 week and 52 week follow-up visits
Measure Participants	149	80
12 Week Visit	118 145.7%	9 5.6%
24 Week Visit	123 151.9%	5 3.1%
52 Week Visit	111 137%	3 1.9%

5. Other Pre-specified Outcome

Title	Exploratory Endpoint: WPAI at 6,12,24,52 Weeks
Description	Evaluation of subjects' work and activity impairment before and after treatment in both the investigational arm and the control arm. The Work Productivity and Activity Impairment (WPAI) questionnaire is a 6-question patient-reported general health assessment of productivity and activity impairment. WPAI results are expressed as the percentage of impairment from 0 to 100 where higher numbers indicate greater impairment or less productivity. Due to an error in the WPAI electronic data collection form, 2 questions were not visible to many subjects resulting in a significant amount of missing data for all scores except non-work activity impairment. Therefore, only the non-work activity impairment results are presented. As MM subjects were allowed to receive a crossover procedure after their 6-week follow-up visit, there is a limited number of MM subjects who completed the 12/24/52 visits.
Time Frame	6,12,24,52 Week Follow-Up

Outcome Measure Data

Analysis Population Description

Per-Protocol Cohort: All randomized subjects expect those who: • Did not complete a baseline or respective follow-up assessment for the time point under analysis • Did not receive the treatment for which they were randomized • Had any major protocol deviation(s)

Arm/Group Title	Randomized ETBC	Randomized MM
Arm/Group Description	Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)	Subjects enrolled and randomized to treatment with medical management (MM) only. Subjects randomized to the MM arm were allowed the option to cross-over to have a procedure with the ETBC after completion of the 6 week follow-up visit. Cross-over subject were followed to 12 weeks post-procedure only. Thereafter, they were exited from the study and not required to undergo the 24 week and 52 week follow-up visits
Measure Participants	149	80
Baseline	45.3 (32.8)	50.4 (31.1)
6 Week Visit	16.6 (23.6)	47.1 (32.0)
12 Week Visit	10.9 (16.1)	38.2 (27.5)
24 Week Visit	12.0 (19.5)	33.8 (37.0)
52 Week Visit	9.1 (18.2)	17.5 (20.6)

Adverse Events

Time Frame	Adverse events were collected for the procedure and at each follow-up visit at 2 weeks, 6 weeks, 12 weeks, 24 weeks, and 52 weeks post-treatment
Adverse Event Reporting Description	AEs in MM subjects prior to crossover are reported in the "Medical Management" arm (n=80). AEs in MM subjects after a crossover ETBC procedure are reported in the "Crossover MM" arm (n=70). To provide a robust safety profile, events are additionally presented in an "ALL ETBC" safety cohort, which consists of all subjects treated with the ETBC in the lead-in phase (n=80), randomized ETBC arm (n=149), and randomized MM arm who crossed over (n=70) for a total of 299 subjects in the "ALL ETBC" arm.
Arm/Group Title	Lead-In		Randomized ETBC		Crossover MM		ALL ETBC		Randomized MM
Arm/Group Description	Subjects enrolled in the Lead-in group and treated with the ETBC		Subjects enrolled and randomized to treatment with the Eustachian Tube Balloon Catheter (ETBC) plus Medical Management (MM)		Subjects enrolled and randomized to treatment with Medical Management (MM) only who crossed over to have treatment with the ETBC after the 6-week follow-up visit		All subjects in the lead-in phase, subjects randomized to the investigational arm who received treatment with the ETBC, and subjects in the control arm who crossed over to have treatment with the ETBC		Subjects enrolled and randomized to treatment with Medical Management (MM) only
All Cause Mortality
	Lead-In		Randomized ETBC		Crossover MM		ALL ETBC		Randomized MM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		1/149 (0.7%)		0/70 (0%)		1/299 (0.3%)		0/80 (0%)
Serious Adverse Events
	Lead-In		Randomized ETBC		Crossover MM		ALL ETBC		Randomized MM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/80 (2.5%)		5/149 (3.4%)		0/70 (0%)		7/299 (2.3%)		1/80 (1.3%)
Cardiac disorders
Coronary artery occlusion	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Myocardial infarction	0/80 (0%)	0	2/149 (1.3%)	2	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
General disorders
Non-cardiac chest pain	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Injury, poisoning and procedural complications
Pelvic fracture	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Syncope	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Psychiatric disorders
Bipolar I disorder	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Other (Not Including Serious) Adverse Events
	Lead-In		Randomized ETBC		Crossover MM		ALL ETBC		Randomized MM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/80 (37.5%)		58/149 (38.9%)		20/70 (28.6%)		108/299 (36.1%)		18/80 (22.5%)
Cardiac disorders
Coronary artery disease	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Ear and labyrinth disorders
Conductive deafness	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Deafness	0/80 (0%)	0	2/149 (1.3%)	3	0/70 (0%)	0	2/299 (0.7%)	3	0/80 (0%)	0
Ear discomfort	2/80 (2.5%)	3	2/149 (1.3%)	2	0/70 (0%)	0	4/299 (1.3%)	5	0/80 (0%)	0
Ear pain	0/80 (0%)	0	4/149 (2.7%)	4	1/70 (1.4%)	1	5/299 (1.7%)	5	1/80 (1.3%)	1
Eustachian tube disorder	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Eustachian tube dysfunction	0/80 (0%)	0	3/149 (2%)	4	0/70 (0%)	0	3/299 (1%)	4	0/80 (0%)	0
Eustachian tube obstruction	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Eustachian tube patulous	0/80 (0%)	0	2/149 (1.3%)	2	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Hypoacusis	1/80 (1.3%)	1	1/149 (0.7%)	1	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Middle ear effusion	0/80 (0%)	0	2/149 (1.3%)	2	2/70 (2.9%)	2	4/299 (1.3%)	4	0/80 (0%)	0
Otorrhea	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Tinnitus	0/80 (0%)	0	1/149 (0.7%)	1	1/70 (1.4%)	1	2/299 (0.7%)	2	0/80 (0%)	0
Tympanic membrane perforation	0/80 (0%)	0	4/149 (2.7%)	4	1/70 (1.4%)	1	5/299 (1.7%)	5	1/80 (1.3%)	1
Vertigo	1/80 (1.3%)	1	2/149 (1.3%)	2	0/70 (0%)	0	3/299 (1%)	3	1/80 (1.3%)	1
Tympanic membrane disorder	0/80 (0%)	0	1/149 (0.7%)	1	1/70 (1.4%)	1	2/299 (0.7%)	2	0/80 (0%)	0
Gastrointestinal disorders
Oesophageal spasm	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Tooth impacted	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Gastroesophageal reflux disease	2/80 (2.5%)	2	1/149 (0.7%)	1	0/70 (0%)	0	3/299 (1%)	3	0/80 (0%)	0
Glossodynia	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Inguinal hernia	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Toothache	2/80 (2.5%)	2	0/149 (0%)	0	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Vomiting	0/80 (0%)	0	0/149 (0%)	0	1/70 (1.4%)	1	1/299 (0.3%)	1	0/80 (0%)	0
General disorders
Adverse drug reaction	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Effusion	1/80 (1.3%)	2	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	2	0/80 (0%)	0
Facial pain	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Oedema	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Pyrexia	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Sensation of foreign body	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Infections and infestations
Herpes zoster	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
tooth abscess	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Viral upper respiratory tract infection	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Acute sinusitis	3/80 (3.8%)	3	1/149 (0.7%)	1	0/70 (0%)	0	4/299 (1.3%)	4	1/80 (1.3%)	1
Bronchitis	1/80 (1.3%)	1	1/149 (0.7%)	1	2/70 (2.9%)	2	4/299 (1.3%)	4	1/80 (1.3%)	1
Cellulitis	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Chronic sinusitis	0/80 (0%)	0	1/149 (0.7%)	1	1/70 (1.4%)	1	2/299 (0.7%)	2	0/80 (0%)	0
Conjunctivitis infective	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Ear infection	1/80 (1.3%)	2	1/149 (0.7%)	1	1/70 (1.4%)	1	3/299 (1%)	4	0/80 (0%)	0
Hordeolum	0/80 (0%)	0	0/149 (0%)	0	1/70 (1.4%)	1	1/299 (0.3%)	1	0/80 (0%)	0
Infection	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Influenza	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Myringitis bullous	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Nasopharyngitis	0/80 (0%)	0	1/149 (0.7%)	1	3/70 (4.3%)	4	4/299 (1.3%)	5	1/80 (1.3%)	1
Otitis extrerna	1/80 (1.3%)	1	2/149 (1.3%)	2	0/70 (0%)	0	3/299 (1%)	3	1/80 (1.3%)	1
Otitis media	1/80 (1.3%)	2	4/149 (2.7%)	4	1/70 (1.4%)	1	6/299 (2%)	7	0/80 (0%)	0
Otitis media acute	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Otitis media chronic	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	1/80 (1.3%)	1
Pharyngitis	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Pharyngitis streptococcal	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Pneumonia	2/80 (2.5%)	2	0/149 (0%)	0	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Sinusitis	2/80 (2.5%)	4	7/149 (4.7%)	8	4/70 (5.7%)	4	13/299 (4.3%)	16	2/80 (2.5%)	2
Tonsillitis	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Upper respiratory tract infection	5/80 (6.3%)	6	10/149 (6.7%)	11	6/70 (8.6%)	6	21/299 (7%)	23	0/80 (0%)	0
Injury, poisoning and procedural complications
Deafness traumatic	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Joint injury	2/80 (2.5%)	2	0/149 (0%)	0	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Laceration	1/80 (1.3%)	1	1/149 (0.7%)	1	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Ligament sprain	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Mucosal excoriation	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Tibia fracture	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Investigations
Blood potassium decreased	0/80 (0%)	0	0/149 (0%)	0	1/70 (1.4%)	1	1/299 (0.3%)	1	0/80 (0%)	0
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	0/80 (0%)	0	0/149 (0%)	0	1/70 (1.4%)	1	1/299 (0.3%)	1	0/80 (0%)	0
Myalgia	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Pain in jaw	1/80 (1.3%)	1	1/149 (0.7%)	1	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Periarthritis	0/80 (0%)	0	0/149 (0%)	0	1/70 (1.4%)	1	1/299 (0.3%)	1	0/80 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesteatoma	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Nervous system disorders
Dizziness	2/80 (2.5%)	2	1/149 (0.7%)	1	0/70 (0%)	0	3/299 (1%)	3	0/80 (0%)	0
Headache	0/80 (0%)	0	2/149 (1.3%)	2	0/70 (0%)	0	2/299 (0.7%)	2	0/80 (0%)	0
Hypoaesthesia	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Paraesthesia	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Sinus headache	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	1/80 (1.3%)	1
Syncope	0/80 (0%)	0	0/149 (0%)	0	1/70 (1.4%)	1	1/299 (0.3%)	1	0/80 (0%)	0
Respiratory, thoracic and mediastinal disorders
Sinus congestion	0/80 (0%)	0	0/149 (0%)	0	0/70 (0%)	0	0/299 (0%)	0	1/80 (1.3%)	1
Asthma	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Cough	0/80 (0%)	0	3/149 (2%)	3	0/70 (0%)	0	3/299 (1%)	3	0/80 (0%)	0
Epistaxis	3/80 (3.8%)	3	1/149 (0.7%)	1	0/70 (0%)	0	4/299 (1.3%)	4	1/80 (1.3%)	1
Nasal congestion	2/80 (2.5%)	2	2/149 (1.3%)	2	0/70 (0%)	0	4/299 (1.3%)	4	1/80 (1.3%)	1
Nasal polyps	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Oropharyngeal pain	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Reflux laryngitis	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Rhinitis allergic	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Wheezing	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Skin and subcutaneous tissue disorders
Eczema	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Pruritis	0/80 (0%)	0	1/149 (0.7%)	1	0/70 (0%)	0	1/299 (0.3%)	1	0/80 (0%)	0
Rash	1/80 (1.3%)	1	0/149 (0%)	0	0/70 (0%)	0	1/299 (0.3%)	1	1/80 (1.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.