Clinical Trial Results:
A prospective, multi-center, controlled, double-blind study to evaluate the efficacy and tolerability of a steroid/antibiotic associated treatment following cataract extraction by means of phaco-emulsification.
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Summary
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EudraCT number |
2016-002138-63 |
Trial protocol |
IT |
Global end of trial date |
31 Mar 2020
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Results information
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Results version number |
v2(current) |
This version publication date |
21 May 2021
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First version publication date |
20 Aug 2020
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Other versions |
v1 |
Version creation reason |
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Summary report(s) |
SAP SYNOPSIS 044/SI |
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 |
044-SI
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
SIFI SpA
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Sponsor organisation address |
Via Ercole Patti, 36, Lavinaio (CT), Italy, 95025
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Public contact |
Clinical Development, S.I.F.I. S.p.A., +39 +39-0957922238, claudine.civiale@sifigroup.com
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Scientific contact |
Clinical Development, S.I.F.I. S.p.A., +39 0957922238, claudine.civiale@sifigroup.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Mar 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this trial is to show that the administration of a reduced dose of NETILDEX ™ gel 2 times a day starting on the day of cataract extraction by means of phaco-emulsification and administered until 14 days after surgery is sufficient to obtain a non-inferior efficacy of the NETILDEX ™ eye drops solution administered 4 times a day for the same period.
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Protection of trial subjects |
The study was monitored by an independent Data Safety Monitoring Board (DSMB).
The DSMB could recommend stopping the study for futility, if at least 3 patients (4.5%) in the same Group have grade +3 or more for both cells and flare at the examination with slit lamp and bio-microscopy, at any time during the study.
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Background therapy |
Cataract is an ophthalmic disease that usually affects the elderly population. Cataract surgery with phaco-emulsification is now the most frequently performed intraocular surgical procedure in the developed world. However, differences in surgical technique impact the severity of surgical trauma and post-operative recovery. The amount of post-operative ocular pain and inflammation plays a significant role in the Patient's perception of the surgical success. Several ophthalmic products have been studied in the management of post-surgery ocular inflammation and pain following cataract surgery. Corticosteroids are considered the gold standard for the treatment of ocular inflammation, and their most commonly used route of administration is the topical instillation as eye drops formulation. After topical administration of Dexamethasone, the concentration in the anterior chamber increases and declines within hours, necessitating frequent daily instillations of eye drops for several weeks. This might be associated with compliance issues, particularly in elderly Patients or in individuals with disabilities. A pharmaceutical formulation allowing for a less frequent administration could therefore be an attractive alternative. | ||
Evidence for comparator |
NETILDEX™ eye drops solution, containing Netilmicin Sulfate 4.55 mg (3mg/ml) and Dexamethasone Disodium Phosphate 1.32 mg (1mg/ml), is already available for Patients. A new ophthalmic gel, preservative-free formulation has been developed. This new formulation has been tested in pre-clinical animal studies and in a clinical trial. The new formulation contains Xanthan gum, a high molecular mass polysaccharide approved by the FDA in 1969 for food products. It is used in the product as viscosity enhancer and to give to the product pseudo-plastic characteristics and prolonged ocular retention time. | ||
Actual start date of recruitment |
09 Jan 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Germany: 18
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Country: Number of subjects enrolled |
Italy: 155
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Worldwide total number of subjects |
173
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EEA total number of subjects |
173
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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) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
28
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From 65 to 84 years |
134
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85 years and over |
11
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Recruitment
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Recruitment details |
The enrollement at the investigational sites was stopped at the achievement of 173 randomizzed patients versus the target of 180 randomizzed patients. The rational of this decision is due to the fact that the number of statistically evaluable patients were already reached (160 ITT population patients versus the 130 requested in the protocol ). Ana | ||||||||||||||||||
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Pre-assignment
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Screening details |
Male and female Patients, aged > 40 years, undergoing cataract extraction by means of phaco-emulsification and intra-ocular lens implantation according to inclusion criteria and after to be thoroughly informed about all aspects of the study, including scheduled study visits and activities, and to have signed the informed consent form. | ||||||||||||||||||
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Period 1
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Period 1 title |
overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Investigator, Monitor, Subject, Data analyst | ||||||||||||||||||
Blinding implementation details |
All daily study products will be manufactured in indistinguishable single dose plastic vials, labeled in accordance with hour of administration. In accordance with the double-blind design of the study, daily treatment for patients randomized to group A (NETILDEX™ ophthalmic gel), will be of 2 doses of active treatment and 2 doses of indistinguishable placebo. For blinding purposes, Group B (NETILDEX™ eye drops solution) medications labels will consist in an aluminum envelope for each dose of the
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Netildex Ophthalmic gel | ||||||||||||||||||
Arm description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
NETILDEX™ ophthalmic gel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ear drops, solution in single-dose container
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Routes of administration |
Ophthalmic use
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Dosage and administration details |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery.
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Arm title
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NETILDEX™ eye drops solution | ||||||||||||||||||
Arm description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ear drops, solution in single-dose container
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Routes of administration |
Ophthalmic use
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Dosage and administration details |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 173 patients were enrolled and randomised but 5 of them didn't received the treatment. So the total number at baseline is 168 |
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Baseline characteristics reporting groups
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Reporting group title |
Netildex Ophthalmic gel
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Reporting group description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NETILDEX™ eye drops solution
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Reporting group description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ITT population
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The ITT Population is defined as all patients who received 7 days of study treatment and had the SLIT lamp examination at baseline visit3 (day 1) and endpoint visit 4 (day 7)
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Subject analysis set title |
The Safety Analysis Population
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety analysis population is defined as all patients registered, who received at least one dose of study treatment
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Subject analysis set title |
The Per-Protocol (PP) populations
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Per-Protocol Population is defined as all subjects of the ITT population who completed regularly the study with no major violations of the eligibility criteria or during study conduction
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End points reporting groups
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Reporting group title |
Netildex Ophthalmic gel
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Reporting group description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery. | ||
Reporting group title |
NETILDEX™ eye drops solution
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Reporting group description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery. | ||
Subject analysis set title |
ITT population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The ITT Population is defined as all patients who received 7 days of study treatment and had the SLIT lamp examination at baseline visit3 (day 1) and endpoint visit 4 (day 7)
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Subject analysis set title |
The Safety Analysis Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety analysis population is defined as all patients registered, who received at least one dose of study treatment
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Subject analysis set title |
The Per-Protocol (PP) populations
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The Per-Protocol Population is defined as all subjects of the ITT population who completed regularly the study with no major violations of the eligibility criteria or during study conduction
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End point title |
Measurement of Inflammation Conditions in the Anterior Ocular Chamber After Cataract Extraction Through Slit Lamp and Bio-microscopy | ||||||||||||||||||
End point description |
the primary efficacy variable is the measurement of inflammation (cellularity and flare) at endpoint (V4), in the anterior ocular chamber, after cataract extraction, examined with slit lamp and bio-microscopy.
Based on these two measurements, a Patient is defined as:
Full responder: if both cellularity and flare are of degree zero Partial responder: if at least one of the two measurements (cellularity and flare) is of degree zero The difference of Full responders after 7 days from surgery has been analysed for non-inferiority of NETILDEX™ Ophthalmic Gel using a non-inferiority margin of -0.10 and a Confidence Interval of 97.5%.
No responder: if both cellularity and flare are greater than zero
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End point type |
Primary
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End point timeframe |
Throughout study completion, approximately 9 weeks.
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| Notes [1] - ITT Population [2] - ITT Population |
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Statistical analysis title |
Measurement of Inflammation | ||||||||||||||||||
Statistical analysis description |
The primary analysis compares the ITT population (Full responder) of NETILDEX™ Ophthalmic Gel (n=80 patients) and NETILDEX™ Eye Drops (n=80 patients).
The difference of Full responders after 7 days from surgery has been analysed for non-inferiority of NETILDEX™ Ophthalmic Gel using a non-inferiority margin of -0.10 and a Confidence Interval of 97.5%. The primary analysis compares the ITT population of NETILDEX™ Ophthalmic Gel (n=80 patients) and NETILDEX™ Eye Drops (n=80 patients).
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Comparison groups |
Netildex Ophthalmic gel v NETILDEX™ eye drops solution
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Number of subjects included in analysis |
160
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||||||||
P-value |
< 0.025 [4] | ||||||||||||||||||
Method |
Confidence Interval | ||||||||||||||||||
Parameter type |
Discrete (counting) variable | ||||||||||||||||||
Confidence interval |
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level |
97.5% | ||||||||||||||||||
sides |
1-sided
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lower limit |
-0.058 | ||||||||||||||||||
upper limit |
0.158 | ||||||||||||||||||
| Notes [3] - The efficacy parameter utilized has been the combination of two clinical parameters, Flare and Cellularity The non inferiority test results indicate that the GEL Group is noninferior to the DROP Group since the lower linmit of the 97.5% Confidence Interval is Greater than the noninferiority limit of -0.10. [4] - The hypotheses for noninferiority has been stated in terms of the difference in the proportions D = ptest − pctrl where test is Netildex gel and ctrl is Netildex drops solution. The null and alternative hypotheses are the following: H0: D = ptest |
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End point title |
Microbial load measurement | |||||||||
End point description |
Microbial load measurement (for Patients with risk of ocular infections, based on Investigator's judgment) through ocular swab, evaluating the antibiotic efficacy 24 hours after surgery, based on the number of detected microbial infections (presence of positive swabs and anti-biogram results, if any).
The anti-biogram should be performed according to standard procedure at investigational sites, but including at least the test with Netilmicin and Cefuroxime.
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End point type |
Secondary
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End point timeframe |
Throughout study completion, approximately 9 weeks.
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| Notes [5] - Safety Population [6] - Safety population |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Assessment of a Potential Variation in the Intra-ocular Pressure Related to the Use of the Gel Formulation Compared to the Eye-drops Formulation, Through Its Measurement Before and After Treatment. | ||||||||||||||||||||||||
End point description |
IOP was measured in both eyes at Visit 1 (Screening examination), Visit 3 (Day 1), Visit 4 (Day 7±1), Visit 5 (Day 15±2) and Visit 6 (Day 60±3) by using a Goldman applanation tonometer (average of two measurements), recording of the time of measurement. All IOP measurements on the same patient will be performed by the same physician with the same tonometer.
Intra-ocular pressure data (change from visit 1) has been tabulated with central and dispersion variables before and after treatment.
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End point type |
Secondary
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End point timeframe |
Throughout study completion, approximately 9 weeks.
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| Notes [7] - Safety population [8] - Safety Population |
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Statistical analysis title |
Intra-ocular pressure (change from visit 1) | ||||||||||||||||||||||||
Statistical analysis description |
Evaluation of intra-ocular pressure (change from Visit 1):
tabulated with central and dispersion variables before and after treatment along with one-sided 97.5% confidence interval of the difference.
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Comparison groups |
Netildex Ophthalmic gel v NETILDEX™ eye drops solution
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Number of subjects included in analysis |
168
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Analysis specification |
Pre-specified
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Analysis type |
other [9] | ||||||||||||||||||||||||
P-value |
= 0.4758 [10] | ||||||||||||||||||||||||
Method |
t-test, 1-sided | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.2238
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Confidence interval |
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level |
97.5% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-0.3944 | ||||||||||||||||||||||||
upper limit |
0.8419 | ||||||||||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.3131
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| Notes [9] - Student's t test for independent samples [10] - The p-value of the difference between The two groups is 0.4758, so we do not reject the null hypothesis TIPO DI VARIABLE ESTIMATE: CONTINUE VARIABLE |
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End point title |
Evaluation of Clinical Signs and Symptoms of Ocular Inflammation | |||||||||||||||||||||
End point description |
Evaluation of ocular inflammation signs/symptoms during the study (other than flare and cellularity) - Total score
•Scoring System for Conjunctival hyperemia. 0 none
1.mild (some vessel injected)
2.moderate (diffuse injection, individual vessels discernible)
3.severe (intense injection, individual vessels not easily discernible)
•Scoring System for Corneal edema and Lid edema. 0 none
1.mild
2.moderate
3.severe
•Scoring System for Ocular discomfort (pain, photophobia, tearing). 0 none
1.mild (present but not distressing)
2.moderate (distressing but not interfering with daily life)
3.severe (very distressing and interfering with daily life)
Evaluation of ocular inflammation signs/symptoms during the study - Total score Safety sample - change from Day 1 It is reported below the number of patients with none discomfort
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End point type |
Secondary
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End point timeframe |
Throughout study completion, approximately 9 weeks.
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| Notes [11] - Safety Population Visit V3: 83 patients analysed Visit 4 82 patients analysed Visit 5: 81 patient [12] - Safety Population Visit 3: 83 patient analysed Visit 4 and Visit 5: 82 patients analysed |
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Statistical analysis title |
Evaluation of Clinical Signs and Symptoms of Ocula | |||||||||||||||||||||
Comparison groups |
Netildex Ophthalmic gel v NETILDEX™ eye drops solution
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Number of subjects included in analysis |
168
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Analysis specification |
Pre-specified
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Analysis type |
other [13] | |||||||||||||||||||||
P-value |
= 0.9392 [14] | |||||||||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
0.0122
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Confidence interval |
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level |
97.5% | |||||||||||||||||||||
sides |
2-sided
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lower limit |
-0.2734 | |||||||||||||||||||||
upper limit |
0.2978 | |||||||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.9261
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| Notes [13] - It has been verified the non significative diffeence between both groups [14] - The p-value of the difference between the two groups is 0.9329 so we do not reject the null hypothesis Tipo di variable estimate: continue variable |
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End point title |
Evaluation of Visual Acuity Through Standard Measurement Systems. | ||||||||||||||||||||||||
End point description |
Visual acuity with correction (best corrected visual acuity) was measured in the operated eye at Screening, Visit 3 (Day 1), Visit 4 (Day 7±1), Visit 5 (Day 15±2) and Visit 6 (Day 60±3). No relevant difference along the study and between treatment groups are present
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End point type |
Secondary
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End point timeframe |
Throughout study completion, approximately 9 weeks.
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Statistical analysis title |
Evaluation of Visual Acuity | ||||||||||||||||||||||||
Statistical analysis description |
Visual acuity with correction (best corrected visual acuity) was measured in both eyes at Visit 1 (Screening examination), and in the operated eye only at Visit 3 (Day 1), Visit 4 (Day 7±1), Visit 5 (Day 15±2) and Visit 6 (Day 60±3). Dilated ophthalmoscopy was performed in the affected eye only at Screening examination (Visit 1/up to Day 0) and at Visit 3 (Day 1), Visit 4 (Day 7±1), Visit 5 (Day 15±2) and Visit 6 (Day 60±3).
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Comparison groups |
NETILDEX™ eye drops solution v Netildex Ophthalmic gel
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Number of subjects included in analysis |
165
|
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Analysis specification |
Pre-specified
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Analysis type |
[15] | ||||||||||||||||||||||||
P-value |
= 0.3823 [16] | ||||||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.0131
|
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Confidence interval |
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level |
97.5% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-0.0761 | ||||||||||||||||||||||||
upper limit |
0.05 | ||||||||||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.201
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| Notes [15] - Student's t for independent samples [16] - The p-value of the difference between the two groups is 0.6823, so we do not reject the null hypothesis |
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End point title |
Evaluation of the Global Tolerability of NETILDEX™ Ophthalmic Gel in Treated Patients (by the Investigator), Through a Standard Questionnaire. | ||||||||||||||||||||||||
End point description |
This outcome was assessed by interviewing the patients about their symptoms (such as burning, stinging and itching) experienced at at Visit 3 (Day 1), Visit 4 (Day 7±1) and Visit 5 (Day 15±2). These symptoms were individually assessed by using a 0 to 3 categorical rating scale.
Changes in Burning, stinging and itching compared to Day 1 Burning/stinging/blurred vision scores: (0) none; (1) mild (present but not distressing); (2) moderate (distressing but not interfering with daily life); (3) severe (very distressing and interfering with daily life)
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End point type |
Secondary
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End point timeframe |
Within 2 weeks after cataract surgery.Global subjective tolerability score at day 15 after surgery day.
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| Notes [17] - Safety population [18] - Safety Population |
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Statistical analysis title |
Evaluation of the Global Tolerability | ||||||||||||||||||||||||
Statistical analysis description |
The global subjective tolerability was assessed at Visit 3 (Day 1), Visit 4 (Day 7±1) and Visit 5 (Day 15±2) interviewing the subject on his/her global sensation and asking to rate using a 0 to 3 categorical scale, as follow:
Score Evaluation
Score Evaluation
0 none
1 mild (present but not distressing)
2 moderate (distressing but not interfering with daily life)
3 severe (very distressing and interfering with daily life)
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Comparison groups |
Netildex Ophthalmic gel v NETILDEX™ eye drops solution
|
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Number of subjects included in analysis |
168
|
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Analysis specification |
Pre-specified
|
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Analysis type |
other [19] | ||||||||||||||||||||||||
P-value |
= 1 [20] | ||||||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||||||
Parameter type |
Odds ratio (OR) | ||||||||||||||||||||||||
Confidence interval |
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| Notes [19] - Comparison between groups of the frequency distributions for the categories decreased/unchanged Fisher's Exact test for the presence of cells with values <5 Categorical variable parameter estimate................: Odds Ratio NOT ESTIMABLE CI (sides, lower and upper limits): NOT ESTIMABLE variability estimate..............: NOT ESTIMABLE dispersion value..................: NOT ESTIMABLE [20] - The p-value of the difference between the two groups is 1.0000, so we do not reject the null hypothesis Tipo di parameter estimate: Comparison between groups of the frequency distributions for the categories decreased/unchanged |
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End point title |
Evaluation of the Safety of NETILDEX™ Ophthalmic Gel Through the Collection and Evaluation of Adverse Events. | |||||||||
End point description |
Ten patients out of 168 experienced at least one AE: on NETILDEX™ Eye Drops. All adverse events were assessed by the investigators as mild or moderate and properly documented in source documents and eCRF. All AE were already known and all patients apart one completed the study.
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End point type |
Secondary
|
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End point timeframe |
Throughout study completion, approximately 9 weeks.
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| Notes [21] - Safety Population [22] - Safety Population |
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Statistical analysis title |
Evaluation of the Adverse Events | |||||||||
Statistical analysis description |
Safety evaluation will include assessments of frequency and severity of adverse events, clinically-significant laboratory abnormalities and physical examination findings.
Comparison between groups of the frequency distributions for the categories presence/absence AE
|
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Comparison groups |
Netildex Ophthalmic gel v NETILDEX™ eye drops solution
|
|||||||||
Number of subjects included in analysis |
168
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other [23] | |||||||||
P-value |
= 0.5325 [24] | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.5779
|
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Confidence interval |
||||||||||
level |
97.5% | |||||||||
sides |
2-sided
|
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lower limit |
0.4287 | |||||||||
upper limit |
5.8075 | |||||||||
| Notes [23] - Fisher's Exact test for the presence of cells with values <5 [24] - The p-value of the difference between the two groups is 0.5325, so we do not reject the null hypothesis |
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Adverse events information
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Timeframe for reporting adverse events |
Overall Trial and 2 months follow-up after day of surgery
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Adverse event reporting additional description |
MedDRA (10.0)
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
|
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Reporting groups
|
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Reporting group title |
NETILDEX™ Ophthalmic Gel
|
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Reporting group description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery. Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery. NETILDEX™ ophthalmic gel: 1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) ophthalmic gel immediately after the surgery then 1 drop twice daily (b.i.d.) from Day 1 until Day 14 after surgery + 1 drop of XANTERGEL™ ophthalmic gel twice daily (b.i.d.) from Day 1 until Day 14 after surgery. Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
NETILDEX™ Eye Drops Solution
|
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Reporting group description |
1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery. Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery. NETILDEX™ eye drops solution: 1 drop of NETILDEX™ (Netilmicin Sulfate 3mg/ml / Dexamethasone Disodium Phosphate 1mg/ml) eye drops solution immediately after the surgery then 1 drop four times a day (q.i.d.) from Day 1 until Day 14 after surgery. Bromfenac 0.9 mg/ml 1 drop twice daily (b.i.d.) for 3 days before cataract surgery | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 4.76% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
16 Feb 2017 |
Protocol version 2.0 (16 February 2017) has been implemented according to the requests raised by the German Competent Authority (BfArM) on the 27th December 2016. |
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Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
