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Pharmacodynamics of Tafluprost 0.0015% Eye Drops: a Comparison Between the Preserved and Unpreserved Formulation

This study has been completed.
Sponsor:
Information provided by:
Santen Oy
ClinicalTrials.gov Identifier:
NCT00918346
First received: June 9, 2009
Last updated: December 10, 2010
Last verified: December 2010
History of Changes
Results First Received: August 4, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Crossover Assignment;   Masking: Single Blind (Investigator);   Primary Purpose: Treatment
Conditions: Open-Angle Glaucoma
Ocular Hypertension
Intervention: Drug: Tafluprost 0.0015%

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

At 2 centers in Germany, 1 center in Finland:

14 September 2005 first patient screened 08 November 2005 first patient randomized 05 April 2006 last patient completed

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 45 patients screened and 43 patients randomized. 2 screening failure patients: 1 withdrawn consent and 1 too low IOP (inclusion criterion 4).

Reporting Groups
  Description
Preserved Formulation First, Then Unpreserved Formulation Tafluprost 0.0015% preserved formulation once daily for first 4 weeks, then unpreserved formulation (after washout)
Unpreserved Formulation First, Then Preserved Formulation Tafluprost 0.0015% unpreserved formulation once daily for first 4 weeks, then preserved formulation (after washout)

Participant Flow for 4 periods

 Period 1:   First Treatment Period (4 Weeks)
    Preserved Formulation First, Then Unpreserved Formulation     Unpreserved Formulation First, Then Preserved Formulation  
STARTED     21     22  
COMPLETED     21     21 [1]
NOT COMPLETED     0     1  
Lack of Efficacy                 0                 1  
[1] A patient completed the first treatment period but discontinued thereafter (did not start washout).

Period 2:   Washout (at Least 4 Weeks)
    Preserved Formulation First, Then Unpreserved Formulation     Unpreserved Formulation First, Then Preserved Formulation  
STARTED     21     21  
COMPLETED     21     21  
NOT COMPLETED     0     0  

Period 3:   Second Treatment Period (4 Weeks)
    Preserved Formulation First, Then Unpreserved Formulation     Unpreserved Formulation First, Then Preserved Formulation  
STARTED     21     21  
COMPLETED     21     21  
NOT COMPLETED     0     0  

Period 4:   Post Study Period
    Preserved Formulation First, Then Unpreserved Formulation     Unpreserved Formulation First, Then Preserved Formulation  
STARTED     21     21  
COMPLETED     21     21  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Reporting Groups
  Description
Entire Study Population Includes all 43 randomized patients (86 eyes)

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
 		  43  
Age  
[units: years]
Mean ± Standard Deviation 		  65.3  ± 10.1  
Gender  
[units: participants]
 		 
Female     27  
Male     16  
Race/Ethnicity, Customized  
[units: participants]
 		 
Caucasian     43  
Region of Enrollment  
[units: participants]
 		 
Germany     32  
Finland     11  
Diagnosis - worse eyes [1]
[units: eyes]
 		 
Primary Open Angle Glaucoma     28  
Capsular Glaucoma     3  
Ocular Hypertension     12  
Central corneal thickness  
[units: micrometer]
Mean ± Standard Deviation 		 
Right eye     548.7  ± 42.8  
Left eye     547.0  ± 45.4  
[1] Worse eye: If both eyes satisfied the inclusion criteria, then the worse eye was the eye with the higher intraocular pressure at the 8:00 IOP measurement at the first baseline visit. In case both eyes had the same IOP, then the right eye was designated as the worse eye. If only one eye satisfied the inclusion criteria, then that eye was considered to be the worse eye.



  Outcome Measures
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1.  Primary:   Intraocular Pressures (IOPs) at Baseline   [ Time Frame: Baseline ]
  Show Outcome Measure 1

2.  Primary:   Intraocular Pressures (IOPs) at Week 1   [ Time Frame: Week 1 ]
  Show Outcome Measure 2

3.  Primary:   Intraocular Pressures (IOPs) at Week 4   [ Time Frame: Week 4 ]
  Show Outcome Measure 3

4.  Primary:   Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)   [ Time Frame: Baseline - Week 4 ]
  Hide Outcome Measure 4

Measure Type Primary
Measure Title Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)
Measure Description Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurements analysis of covariance (RM ANCOVA) model.
Time Frame Baseline - Week 4  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention To Treat (ITT): randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.

Reporting Groups
  Description
RM ANCOVA: ITT Efficacy Dataset randomized who received at least one dose of study medication and had at least one IOP measurement

Measured Values
    RM ANCOVA: ITT Efficacy Dataset  
Number of Participants Analyzed  
[units: participants]
 		  43  
Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)  
[units: mmHg]
Mean ( 95% Confidence Interval ) 		  0.01  
  ( -0.46 to 0.49 )  


Statistical Analysis 1 for Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)
Groups [1] RM ANCOVA: ITT Efficacy Dataset
Non-Inferiority/Equivalence Test [2] Yes
Method [3] ANCOVA
P Value [4] 0.96
Mean Difference (Final Values) [5] 0.01
95% Confidence Interval ( -0.46 to 0.49 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  H1 (the alternative hypothesis aimed to be proven): the unpreserved formulation is equivalent with the preserved formulation
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  The equivalence limit was set to 1.5 mmHg. Equivalence was shown if the two-sided 95% confidence interval for the difference (unpreserved-preserved) lay entirely within the equivalence range (-1.5 mmHg, 1.5 mmHg). Target sample size was 34 evaluable patients (40 randomized), assuming a standard deviation of 3.0 mmHg change in IOP, a power of 80%, an intra-class correlation coefficient of 0.60 and a twosided type 1 error rate of 5%.
[3] Other relevant information, such as adjustments or degrees of freedom:
  Baseline IOP a covariate
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  Analysis model used IOP measurements at four timepoints (at 8, 12, 16 and 20 o'clock) on Baseline and Week 4.



5.  Primary:   Primary Pharmacodynamic Variable Per Protocol Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)   [ Time Frame: Baseline - Week 4 ]
  Show Outcome Measure 5

6.  Secondary:   Overall and Time-wise Comparisons of IOP at Week 1   [ Time Frame: Baseline - Week 1 ]
  Show Outcome Measure 6

7.  Secondary:   Change From Baseline in Time-wise IOPs at Week 4   [ Time Frame: Baseline - Week 4 ]
  Show Outcome Measure 7


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked 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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked 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.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Auli Ropo
Organization: Santen Oy
phone: +358405012416
e-mail: auli.ropo@santen.fi


No publications provided


Responsible Party: Auli Ropo, MD, PhD, Santen Oy
ClinicalTrials.gov Identifier: NCT00918346     History of Changes
Other Study ID Numbers: 77550
Study First Received: June 9, 2009
Results First Received: August 4, 2009
Last Updated: December 10, 2010
Health Authority: Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices