Clinical Trial Results:
A Multicenter, Double-masked, Randomized, Active-controlled, Parallel Study of the Safety
and Efficacy of Once-daily Bimatoprost Preservative-free Ophthalmic Solution Compared
to Twice-daily Timolol Ophthalmic Solution in Paediatric Patients with Glaucoma
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Summary
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EudraCT number |
2011-003278-10 |
Trial protocol |
FR GB DE |
Global end of trial date |
30 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Mar 2016
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First version publication date |
06 Mar 2016
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Other versions |
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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 |
192024-056
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01426113 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Allergan Limited
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Sponsor organisation address |
Allergan Limited Marlow International The Parkway, Marlow, Buckinghamshire, United Kingdom, SL7 1YL
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Public contact |
Allergan Limited EU Regulatory Dept, Allergan Limited, 44 1628 494444, ml-eu_reg_affairs@allergan.com
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Scientific contact |
Allergan Limited EU Regulatory Dept, Allergan Limited, 44 1628 494444, ml-eu_reg_affairs@allergan.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000917-PIP01-10 | ||
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 |
20 Jan 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Oct 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Oct 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 primary objective of the study was to evaluate the safety and IOP-lowering efficacy of
once-daily bimatoprost ophthalmic solution compared with twice-daily timolol ophthalmic solution for 12 weeks in pediatric patients with glaucoma.
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Protection of trial subjects |
Parent(s) or legal guardian(s) were required to read and sign an Informed Consent Form. Subjects may have signed an assent, if applicable, prior to any study procedures being performed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Sep 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
9 Months | ||
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 |
United Kingdom: 1
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
Taiwan: 1
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Country: Number of subjects enrolled |
United States: 3
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Worldwide total number of subjects |
6
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EEA total number of subjects |
2
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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) |
6
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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 |
The study was discontinued prematurely after enrollment of 6 patients. | ||||||||||||||||||
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Pre-assignment
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Screening details |
The Screening period was from Day -28 to Day -2. All randomized patients are noted in the overall study period. | ||||||||||||||||||
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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 |
Double blind | ||||||||||||||||||
Roles blinded |
Investigator, Carer, Subject | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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bimatoprost ophthalmic solution formulation A and vehicle | ||||||||||||||||||
Arm description |
1 drop bimatoprost vehicle in the affected eye(s) in the morning and 1 drop of bimatoprost ophthalmic solution formulation A in the affected eye(s) in the evening for 6 weeks, followed by 1 drop bimatoprost ophthalmic solution formulation A in the affected eye(s) in the morning and 1 drop bimatoprost vehicle in the affected eye(s) in the evening for 6 additional weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
bimatoprost
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Eye drops
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Routes of administration |
Ocular use
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Dosage and administration details |
1 drop bimatoprost vehicle in the affected eye(s) in the morning and 1 drop of bimatoprost ophthalmic solution formulation A in the affected eye(s) in the evening for 6 weeks, followed by 1 drop bimatoprost ophthalmic solution formulation A in the affected eye(s) in the morning and 1 drop bimatoprost vehicle in the affected eye(s) in the evening for 6 additional weeks.
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Arm title
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timolol ophthalmic solution | ||||||||||||||||||
Arm description |
1 drop timolol ophthalmic solution in the affected eye(s) in the morning and evening for 12 weeks. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
timolol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Eye drops
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Routes of administration |
Ocular use
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Dosage and administration details |
1 drop timolol ophthalmic solution in the affected eye(s) in the morning and evening for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
bimatoprost ophthalmic solution formulation A and vehicle
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Reporting group description |
1 drop bimatoprost vehicle in the affected eye(s) in the morning and 1 drop of bimatoprost ophthalmic solution formulation A in the affected eye(s) in the evening for 6 weeks, followed by 1 drop bimatoprost ophthalmic solution formulation A in the affected eye(s) in the morning and 1 drop bimatoprost vehicle in the affected eye(s) in the evening for 6 additional weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
timolol ophthalmic solution
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Reporting group description |
1 drop timolol ophthalmic solution in the affected eye(s) in the morning and evening for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
bimatoprost ophthalmic solution formulation A and vehicle
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Reporting group description |
1 drop bimatoprost vehicle in the affected eye(s) in the morning and 1 drop of bimatoprost ophthalmic solution formulation A in the affected eye(s) in the evening for 6 weeks, followed by 1 drop bimatoprost ophthalmic solution formulation A in the affected eye(s) in the morning and 1 drop bimatoprost vehicle in the affected eye(s) in the evening for 6 additional weeks. | ||
Reporting group title |
timolol ophthalmic solution
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Reporting group description |
1 drop timolol ophthalmic solution in the affected eye(s) in the morning and evening for 12 weeks. | ||
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End point title |
Change from Baseline in Intraocular Pressure (IOP) in the Study Eye [1] | ||||||||||||
End point description |
IOP is a measure of the fluid pressure inside the study eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive change from baseline indicates an increase in IOP (worsening). Due to lack of enrollment, analysis was not performed for this outcome measure.
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End point type |
Primary
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End point timeframe |
Baseline, Week 6
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was discontinued after the enrollment of 6 patients; therefore, statistical analyses were not performed. |
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| Notes [2] - Due to lack of enrollment, analysis was not performed for this outcome measure. [3] - Due to lack of enrollment, analysis was not performed for this outcome measure. |
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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 were reported from signing consent through Month 12/Exit.
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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 |
17.1
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Reporting groups
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Reporting group title |
bimatoprost ophthalmic solution formulation A and vehicle
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Reporting group description |
1 drop bimatoprost vehicle in the affected eye(s) in the morning and 1 drop of bimatoprost ophthalmic solution formulation A in the affected eye(s) in the evening for 6 weeks, followed by 1 drop bimatoprost ophthalmic solution formulation A in the affected eye(s) in the morning and 1 drop bimatoprost vehicle in the affected eye(s) in the evening for 6 additional weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
timolol ophthalmic solution
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Reporting group description |
1 drop timolol ophthalmic solution in the affected eye(s) in the morning and evening for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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Date |
Amendment |
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30 Jul 2012 |
1) allow the use of Icare and Perkins tonometers; 2) remove PK sampling at baseline; and 3) change the noninferiority margin for analysis of the primary efficacy variable and update sample size calculations accordingly. |
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19 Apr 2013 |
1) remove evening office visits; 2) change the primary efficacy endpoint to week 6 (hour 2); 3) in the bimatoprost group, change the dosing of bimatoprost to the morning and vehicle to the evening from week 6 to week 12; 4) add a week 8 visit and move pharmacokinetic measurements from week 6 to week 8; 5) change the IOP measurement in weeks 8 and 12 to occur at time 0 (for trough effect); and 6) increase the study sample size to ensure that at least 80 patients were evaluable at weeks 6 and 12 (previous discontinuation rates predicted that approximately 90 patients would be needed to be randomized at baseline, but up to 120 patients could be enrolled if needed). |
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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. | |||
| None reported | |||
