Pharmacodynamics of Tafluprost 0.0015% Eye Drops: a Compa... | NCT00918346

Pharmacodynamics of Tafluprost 0.0015% Eye Drops: a Compa... | NCT00918346 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Tafluprost 0.0015% preserved formulation	Experimental		Drug: Tafluprost 0.0015%
Tafluprost 0.0015% unpreserved formulation	Experimental		Drug: Tafluprost 0.0015%

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Tafluprost 0.0015%	Drug	Eye drops, 0.015 mg/ml, once daily to affected eye(s)	Tafluprost 0.0015% preserved formulation Tafluprost 0.0015% unpreserved formulation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Intraocular Pressures (IOPs) at Baseline	IOPs at baseline: mean IOP values at four timepoints (worse eye)	Baseline
Intraocular Pressures (IOPs) at Week 1	IOPs at week 1: mean IOP values at four timepoints (worse eye)	Week 1
Intraocular Pressures (IOPs) at Week 4	IOPs at week 4: mean IOP values at four timepoints (worse eye)	Week 4
Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)	Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurements analysis of covariance (RM ANCOVA) model.	Baseline - Week 4
Primary Pharmacodynamic Variable Per Protocol Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)	Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurments analysis of covariance (RM ANCOVA) model.	Baseline - Week 4

Secondary Outcomes

Measure	Description	Time Frame
Overall and Time-wise Comparisons of IOP at Week 1	The overall and time-wise, i.e. at 8:00, 12:00, 16:00 and 20:00, comparisons of IOP at week 1 (diurnal IOP and IOP value at given timepoint at 1 week minus corresponding value at baseline: unpreserved-preserved) were done using the RM ANCOVA model.	Baseline - Week 1

Contacts/Locations Module

Name	Affiliation	Role
Juhani Airaksinen, Prof.	University Hospital of Oulu	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Oulu University Hospital		Oulu		90029	Finland
Ulrich Richter's surgery

Arm/Group Information

ID	Title	Description
FG000	Preserved Formulation First, Then Unpreserved Formulation	Tafluprost 0.0015% preserved formulation once daily for first 4 weeks, then unpreserved formulation (after washout)
FG001	Unpreserved Formulation First, Then Preserved Formulation	Tafluprost 0.0015% unpreserved formulation once daily for first 4 weeks, then preserved formulation (after washout)

Periods

Title

Milestones

Reasons Not Completed

First Treatment Period (4 Weeks)

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00122 subjects
COMPLETED		FG00021 subjects FG00121 subjectsA patient completed the first treatment period but discontinued thereafter (did not start washout).
NOT COMPLETED		FG0000 subjects FG0011 subjects

Type	Comment	Reasons
Lack of Efficacy		FG0000 subjects FG0011 subjects

Washout (at Least 4 Weeks)

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00121 subjects
COMPLETED		FG00021 subjects FG001

Second Treatment Period (4 Weeks)

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00121 subjects
COMPLETED		FG00021 subjects FG001

Post Study Period

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00121 subjects
COMPLETED		FG00021 subjects FG001

Baseline Characteristics Module

ID	Title	Description
BG000	Entire Study Population	Includes all 43 randomized patients (86 eyes)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Intraocular Pressures (IOPs) at Baseline

IOPs at baseline: mean IOP values at four timepoints (worse eye)

IOPs of all subjects who received preserved/unpreserved formulation

Posted

Mean

Standard Deviation

mmHg

Baseline

ID	Title	Description
OG000	Preserved Formulation	tafluprost 0.0015% preserved formulation
OG001	Unpreserved Formulation	tafluprost 0.0015% unpreserved formulation

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Preserved Formulation	Tafluprost 0.0015% preserved formulation once daily for 4 weeks

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Conjunctival hyperemia	Eye disorders	MedDRA 8.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Auli Ropo	Santen Oy	+358405012416		auli.ropo@santen.fi

ID	Term
D005902	Glaucoma, Open-Angle
D009798	Ocular Hypertension

ID	Term
D005901	Glaucoma
D005128	Eye Diseases

Diagnosis - worse eyes

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.

Number

eyes

Title

Denominators

Categories

Primary Open Angle Glaucoma

Title	Measurements
	BG00028

Capsular Glaucoma

Title	Measurements
	BG0003

Ocular Hypertension

Title	Measurements
	BG00012

Title

Denominators

Categories

8 o'clock

Title	Measurements
	OG00022.57± 3.04 OG00122.98± 3.18

12 o'clock

Title	Measurements
	OG00020.86± 2.79 OG00121.78± 2.68

16 o'clock

Title	Measurements
	OG00021.73± 3.19 OG00121.51± 2.49

20 o'clock

Title	Measurements
	OG00021.77± 3.02 OG00121.81± 2.61

Secondary

Overall and Time-wise Comparisons of IOP at Week 1

The overall and time-wise, i.e. at 8:00, 12:00, 16:00 and 20:00, comparisons of IOP at week 1 (diurnal IOP and IOP value at given timepoint at 1 week minus corresponding value at baseline: unpreserved-preserved) were done using the RM ANCOVA model.

ITT: randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.

Posted

Mean

95% Confidence Interval

mmHg

Baseline - Week 1

ID	Title	Description
OG000	RM ANCOVA: ITT Efficacy Dataset	randomized and received study medication

Units	Counts
Participants	OG00043

Title

Denominators

Categories

Overall

Title	Measurements
	OG000-0.27(-0.73 to 0.19)

Timepoint 8:00

Title	Measurements
	OG000-0.32(-0.96 to 0.32)

Timepoint 12:00

Secondary

Change From Baseline in Time-wise IOPs at Week 4

The time-wise, i.e. at 8:00, 12:00, 16:00 and 20:00, comparisons of IOP at week 4 (IOP value at given timepoint at 4 weeks minus corresponding value at baseline: unpreserved-preserved) were done using the RM ANCOVA model.

ITT: randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.

Posted

Mean

95% Confidence Interval

mmHg

Baseline - Week 4

ID	Title	Description
OG000	RM ANCOVA: ITT Efficacy Dataset	randomized and received study medication

Units	Counts
Participants	OG00043

Title

Denominators

Categories

Timepoint 8:00

Title	Measurements
	OG0000.24(-0.51 to 0.98)

Timepoint 12:00

Title	Measurements
	OG0000.11(-0.64 to 0.86)

Timepoint 16:00

Primary

Intraocular Pressures (IOPs) at Week 1

IOPs at week 1: mean IOP values at four timepoints (worse eye)

IOPs of all subjects who received preserved/unpreserved formulation

Posted

Mean

Standard Deviation

mmHg

Week 1

ID	Title	Description
OG000	Preserved Formulation	tafluprost 0.0015% preserved formulation
OG001	Unpreserved Formulation	tafluprost 0.0015% unpreserved formulation

Units	Counts
Participants	OG00042 OG00143

Title

Denominators

Categories

8 o'clock

Title	Measurements
	OG00016.43± 2.11 OG00116.21± 2.70

12 o'clock

Title	Measurements
	OG000

Primary

Intraocular Pressures (IOPs) at Week 4

IOPs at week 4: mean IOP values at four timepoints (worse eye)

IOPs of all subjects who received preserved/unpreserved formulation

Posted

Mean

Standard Deviation

mmHg

Week 4

ID	Title	Description
OG000	Preserved Formulation	tafluprost 0.0015% preserved formulation
OG001	Unpreserved Formulation	tafluprost 0.0015% unpreserved formulation

Units	Counts
Participants	OG00042 OG00143

Title

Denominators

Categories

8 o'clock

Title	Measurements
	OG00016.39± 2.43 OG00116.80± 3.00

12 o'clock

Title	Measurements
	OG000

Primary

Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)

Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurements analysis of covariance (RM ANCOVA) model.

Intention To Treat (ITT): randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.

Posted

Mean

95% Confidence Interval

mmHg

Baseline - Week 4

ID	Title	Description
OG000	RM ANCOVA: ITT Efficacy Dataset	randomized who received at least one dose of study medication and had at least one IOP measurement

Units	Counts
Participants	OG00043

Title

Denominators

Categories

Title	Measurements
	OG0000.01(-0.46 to 0.49)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	H1 (the alternative hypothesis aimed to be proven): the unpreserved formulation is equivalent with the preserved formulation	ANCOVA	Baseline IOP a covariate	0.96		Mean Difference (Final Values)	0.01				95	-0.46	0.49			Analysis model used IOP measurements at four timepoints (at 8, 12, 16 and 20 o'clock) on Baseline and Week 4.	Yes	Non-Inferiority or Equivalence	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%.

Primary

Primary Pharmacodynamic Variable Per Protocol Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye)

Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurments analysis of covariance (RM ANCOVA) model.

Per Protocol (PP): randomized patients who completed the study per protocol (i.e. excluded from PP is the discontinued patient and a patient with major protocol violation)

Posted

Mean

95% Confidence Interval

mmHg

Baseline - Week 4

ID	Title	Description
OG000	RM ANCOVA: PP Efficacy Dataset	randomized patients who completed the study per protocol (PP)

Units	Counts
Participants	OG00041

Title

Denominators

Categories

Title	Measurements
	OG000-0.05(-0.52 to 0.42)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	H1 (the alternative hypothesis aimed to be proven): the unpreserved formulation is equivalent with the preserved formulation	ANCOVA	Baseline IOP a covariate	0.83		Median Difference (Final Values)	-0.05				95	-0.52	0.42			Analysis model used IOP measurements at four timepoints (at 8, 12, 16 and 20 o'clock) on Baseline and Week 4	Yes	Non-Inferiority or Equivalence	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 I error rate of 5%.