Clinical Trial Results:
Proof of Concept of Single Application of AL-60371/AL-817 Otic Suspension in Treatment of Acute Otitis Media With Tympanostomy Tubes Compared to CIPRODEX® (BID for 7 Days)
Summary
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EudraCT number |
2017-002689-30 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
19 Aug 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Jan 2018
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First version publication date |
04 Jan 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C-13-026
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01908803 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Alcon Research Ltd
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Sponsor organisation address |
6201 S. Freeway, Fort Worth, Texas, United States, 76134
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Public contact |
Ophthalmology Unit, Novartis Pharmaceuticals , +44 0127666733391, dennis.wong@novartis.com
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Scientific contact |
Ophthalmology Unit, Novartis Pharmaceuticals , +44 0127666733391, dennis.wong@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Aug 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Aug 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Aug 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The purpose of this study is to evaluate a single application of AL-60371/AL-817 Otic Suspension relative to ototopical CIPRODEX for sustained clinical cure, microbiological success, and time to cessation of otorrhea.
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Protection of trial subjects |
Prior to the start of the study, the study protocol, the informed consent and assent documents, patient
instruction sheets, the Investigator’s Brochure, as well as any advertising materials used to recruit
patients were submitted to institutional review boards (IRBs) and independent ethics committees (IECs).
The IRB/IECs reviewed all documents and approved required documents; copies of the approval letters
were provided to Alcon. Consistent with both the IRB/IEC’s requirements and all applicable regulations,
the Investigators periodically provided study updates to the IRB/IEC. A patient or parent/legal guardian
(if necessary, a legally authorized representative) provided informed consent, and children signed an
approved assent form when appropriate. This study was conducted in accordance with Good Clinical
Practices (GCP) and the ethical principles that have their origins in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Dec 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 68
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Worldwide total number of subjects |
68
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
33
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Children (2-11 years) |
35
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited from 12 study centers located in the US. | |||||||||||||||||||||
Pre-assignment
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Screening details |
Of the 84 enrolled, 14 subjects were exited as screen failures prior to randomization. Two randomized subjects discontinued prior to receiving investigational product. | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||||||||||||||
Roles blinded |
Investigator [1] | |||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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AL-60371/AL-817 | |||||||||||||||||||||
Arm description |
200 μL in affected ear(s) through tympanostomy tube on Day 1 (Visit 1) | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
AL-60371/AL-817 otic suspension
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ear drops, suspension
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Routes of administration |
Auricular use
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Dosage and administration details |
200 μL in affected ear(s) through tympanostomy tube on Day 1 (Visit 1)
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Arm title
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CIPRODEX | |||||||||||||||||||||
Arm description |
Four drops in affected ear(s) twice daily through tympanostomy tube for 7 days | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Ciprofloxacin 0.3%/dexamethasone 0.1% otic suspension
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Investigational medicinal product code |
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Other name |
CIPRODEX®
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Pharmaceutical forms |
Ear drops, suspension, Ear drops, suspension
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Routes of administration |
Auricular use, Auricular use
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Dosage and administration details |
Four drops in affected ear(s) twice daily through tympanostomy tube for 7 days
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Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: This was a single-blind trial and only the investigator was masked. |
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Baseline characteristics reporting groups
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Reporting group title |
AL-60371/AL-817
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Reporting group description |
200 μL in affected ear(s) through tympanostomy tube on Day 1 (Visit 1) | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CIPRODEX
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Reporting group description |
Four drops in affected ear(s) twice daily through tympanostomy tube for 7 days | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AL-60371/AL-817
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Reporting group description |
200 μL in affected ear(s) through tympanostomy tube on Day 1 (Visit 1) | ||
Reporting group title |
CIPRODEX
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Reporting group description |
Four drops in affected ear(s) twice daily through tympanostomy tube for 7 days |
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End point title |
Proportion of Subjects With Sustained Clinical Cure at Day 3 Visit | ||||||||||||
End point description |
A sustained clinical cure at Day 3 was attained if otorrhea was absent at the Day 3 visit and continued to be absent through the last study visit (Day 8 or Early Exit). Proportion of subjects is reported as a percentage. This analysis population includes all randomized subjects who received at least 1 dose of investigational product and were culture positive at the Day 1 visit in the study ear.
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End point type |
Primary
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End point timeframe |
Day 3 post-treatment up to Day 8 or Early Exit
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Statistical analysis title |
Sustained Clinical Cure at Day 3 | ||||||||||||
Statistical analysis description |
Descriptive statistics for the difference of the group proportions are provided including the 95% CI.
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Comparison groups |
CIPRODEX v AL-60371/AL-817
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Number of subjects included in analysis |
61
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
6.6
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-18.1 | ||||||||||||
upper limit |
31.4 |
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End point title |
Proportion of Subjects With Microbiological Success at the Day 8 Visit | ||||||||||||
End point description |
Microbiological success was attained if all pre-therapy bacteria were absent in the Day 8 specimen. In a subject with no otorrhea at Day 8, eradication of pre-therapy bacteria was presumed and the subject was considered a microbiological success. This analysis population includes all randomized subjects who received at least 1 dose of investigational product and were culture positive at the Day 1 visit in the study ear.
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End point type |
Secondary
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End point timeframe |
Day 8
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Notes [1] - This outcome measure was not analyzed as a consequence of the study’s early termination. [2] - This outcome measure was not analyzed as a consequence of the study’s early termination. |
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No statistical analyses for this end point |
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End point title |
Median Time (in Days) to Cessation of Otorrhea | ||||||||||||
End point description |
Median time (in days) to the cessation of otorrhea (ie, otorrhea was absent) was calculated as the number of days from the Day 1 (Visit 1) to the absence of otorrhea in the affected ear(s) as recorded by the parent/guardian via the twice-daily diary. Cessation of otorrhea was defined as ending on the first day that otorrhea was absent from the affected ear(s) and remained absent for any/all subsequent diary entries. This analysis population includes all randomized subjects who received at least 1 dose of investigational product and were culture positive at the Day 1 visit in the study ear.
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End point type |
Secondary
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End point timeframe |
Time to event, up to Day 8
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Notes [3] - This outcome measure was not analyzed as a consequence of the study’s early termination. [4] - This outcome measure was not analyzed as a consequence of the study’s early termination. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected for the duration of subject participation in the study (8-10 days).
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Adverse event reporting additional description |
Only total subjects affected by non-serious AEs that occur at >5% are reported.
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Assessment type |
Systematic | |||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
AL-60371/AL-817
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Reporting group description |
Includes all subjects administered a dose of AL-60371/AL-817 | |||||||||||||||||||||
Reporting group title |
CIPRODEX
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Reporting group description |
Includes all subjects administered a dose of CIPRODEX® | |||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Terminated due to management decision. |