Ocular Hypertension, Open-Angle Glaucoma
Conditions
Keywords
Ocular hypertension
Brief summary
The objective of this study is to investigate the pharmacodynamics (as expressed in intraocular pressure \[IOP\]) of two formulations of tafluprost 0.0015% eyedrops (preserved and unpreserved) in patients with open-angle glaucoma or ocular hypertension. The primary aim of this study is to show that IOP reduction between the two formulations is equivalent at the end of the 4 week treatment period.
Interventions
Eye drops, 0.015 mg/ml, once daily to affected eye(s)
Sponsors
Santen Oy
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or more * A diagnosis of open angle glaucoma or ocular hypertension * Prior use of prostaglandin(s) * Intra ocular pressure of 22-34 mmHg in at least one eye
Exclusion criteria
* Females who are pregnant, nursing or planning a pregnancy, or females of childbearing potential who are not using a reliable method of contraception * Previous participation in any clinical trial in which tafluprost was an investigational drug or use of contact lenses at screening or during the study * Presence of any abnormality or significant illness that could be expected to interfere with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressures (IOPs) at Week 1 | Week 1 | IOPs at week 1: mean IOP values at four timepoints (worse eye) |
| Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye) | Baseline - Week 4 | Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurements analysis of covariance (RM ANCOVA) model. |
| Primary Pharmacodynamic Variable Per Protocol Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye) | Baseline - Week 4 | Overall treatment difference at 4 weeks (unpreserved-preserved) evaluated using a repeated measurments analysis of covariance (RM ANCOVA) model. |
| Intraocular Pressures (IOPs) at Baseline | Baseline | IOPs at baseline: mean IOP values at four timepoints (worse eye) |
| Intraocular Pressures (IOPs) at Week 4 | Week 4 | IOPs at week 4: mean IOP values at four timepoints (worse eye) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Time-wise IOPs at Week 4 | Baseline - 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. |
| Overall and Time-wise Comparisons of IOP at Week 1 | Baseline - 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. |
Countries
Finland, Germany
Participant flow
Recruitment details
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
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).
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all 43 randomized patients (86 eyes) | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Treatment Period (4 Weeks) | Lack of Efficacy | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 65.3 years STANDARD_DEVIATION 10.1 |
| Central corneal thickness Left eye | 547.0 micrometer STANDARD_DEVIATION 45.4 |
| Central corneal thickness Right eye | 548.7 micrometer STANDARD_DEVIATION 42.8 |
| Diagnosis - worse eyes Capsular Glaucoma | 3 eyes |
| Diagnosis - worse eyes Ocular Hypertension | 12 eyes |
| Diagnosis - worse eyes Primary Open Angle Glaucoma | 28 eyes |
| Race/Ethnicity, Customized Caucasian | 43 participants |
| Region of Enrollment Finland | 11 participants |
| Region of Enrollment Germany | 32 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 42 | 11 / 43 |
| serious Total, serious adverse events | 0 / 42 | 0 / 43 |
Outcome results
Primary
Intraocular Pressures (IOPs) at Baseline
IOPs at baseline: mean IOP values at four timepoints (worse eye)
Time frame: Baseline
Population: IOPs of all subjects who received preserved/unpreserved formulation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Preserved Formulation | Intraocular Pressures (IOPs) at Baseline | 8 o'clock | 22.57 mmHg | Standard Deviation 3.04 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Baseline | 12 o'clock | 20.86 mmHg | Standard Deviation 2.79 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Baseline | 16 o'clock | 21.73 mmHg | Standard Deviation 3.19 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Baseline | 20 o'clock | 21.77 mmHg | Standard Deviation 3.02 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Baseline | 20 o'clock | 21.81 mmHg | Standard Deviation 2.61 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Baseline | 8 o'clock | 22.98 mmHg | Standard Deviation 3.18 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Baseline | 16 o'clock | 21.51 mmHg | Standard Deviation 2.49 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Baseline | 12 o'clock | 21.78 mmHg | Standard Deviation 2.68 |
Primary
Intraocular Pressures (IOPs) at Week 1
IOPs at week 1: mean IOP values at four timepoints (worse eye)
Time frame: Week 1
Population: IOPs of all subjects who received preserved/unpreserved formulation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 8 o'clock | 16.43 mmHg | Standard Deviation 2.11 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 20 o'clock | 16.26 mmHg | Standard Deviation 2.2 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 12 o'clock | 15.77 mmHg | Standard Deviation 1.6 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 16 o'clock | 16.23 mmHg | Standard Deviation 1.73 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 8 o'clock | 16.21 mmHg | Standard Deviation 2.7 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 16 o'clock | 15.83 mmHg | Standard Deviation 1.99 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 12 o'clock | 15.72 mmHg | Standard Deviation 1.92 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 1 | 20 o'clock | 16.16 mmHg | Standard Deviation 2.08 |
Primary
Intraocular Pressures (IOPs) at Week 4
IOPs at week 4: mean IOP values at four timepoints (worse eye)
Time frame: Week 4
Population: IOPs of all subjects who received preserved/unpreserved formulation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 8 o'clock | 16.39 mmHg | Standard Deviation 2.43 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 12 o'clock | 16.30 mmHg | Standard Deviation 2.46 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 16 o'clock | 16.64 mmHg | Standard Deviation 2.37 |
| Preserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 20 o'clock | 17.21 mmHg | Standard Deviation 1.91 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 20 o'clock | 17.01 mmHg | Standard Deviation 2.44 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 8 o'clock | 16.80 mmHg | Standard Deviation 3 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 16 o'clock | 16.71 mmHg | Standard Deviation 2.53 |
| Unpreserved Formulation | Intraocular Pressures (IOPs) at Week 4 | 12 o'clock | 16.67 mmHg | Standard Deviation 2.54 |
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.
Time frame: Baseline - Week 4
Population: Intention To Treat (ITT): randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Preserved Formulation | Primary Pharmacodynamic Variable Intention to Treat Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye) | 0.01 mmHg |
Comparison: H1 (the alternative hypothesis aimed to be proven): the unpreserved formulation is equivalent with the preserved formulationp-value: 0.9695% CI: [-0.46, 0.49]ANCOVA
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.
Time frame: Baseline - Week 4
Population: 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)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Preserved Formulation | Primary Pharmacodynamic Variable Per Protocol Efficacy Dataset: Change From Baseline in the Overall Diurnal Intraocular Pressure (IOP) at Week 4 (Worse Eye) | -0.05 mmHg |
Comparison: H1 (the alternative hypothesis aimed to be proven): the unpreserved formulation is equivalent with the preserved formulationp-value: 0.8395% CI: [-0.52, 0.42]ANCOVA
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.
Time frame: Baseline - Week 4
Population: ITT: randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Preserved Formulation | Change From Baseline in Time-wise IOPs at Week 4 | Timepoint 8:00 | 0.24 mmHg |
| Preserved Formulation | Change From Baseline in Time-wise IOPs at Week 4 | Timepoint 12:00 | 0.11 mmHg |
| Preserved Formulation | Change From Baseline in Time-wise IOPs at Week 4 | Timepoint 16:00 | 0.00 mmHg |
| Preserved Formulation | Change From Baseline in Time-wise IOPs at Week 4 | Timepoint 20:00 | -0.30 mmHg |
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.
Time frame: Baseline - Week 1
Population: ITT: randomized patients who received at least one dose of study medication and had at least one pharmacodynamic (IOP) measurement available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Preserved Formulation | Overall and Time-wise Comparisons of IOP at Week 1 | Timepoint 8:00 | -0.32 mmHg |
| Preserved Formulation | Overall and Time-wise Comparisons of IOP at Week 1 | Overall | -0.27 mmHg |
| Preserved Formulation | Overall and Time-wise Comparisons of IOP at Week 1 | Timepoint 12:00 | -0.25 mmHg |
| Preserved Formulation | Overall and Time-wise Comparisons of IOP at Week 1 | Timepoint 16:00 | -0.39 mmHg |
| Preserved Formulation | Overall and Time-wise Comparisons of IOP at Week 1 | Timepoint 20:00 | -0.13 mmHg |