Safety and Efficacy of PF-04217329 in Patients With Glaucoma or Elevated Eye Pressure.

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of PF-04217329.

Official Title
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A 2-STAGE, PHASE 2, DOUBLE-MASKED, RANDOMIZED, VEHICLE CONTROLLED, DOSE RESPONSE TRIAL OF PF-04217329 AND THE MARKETED FORMULATION OF LATANOPROST IN PATIENTS WITH PRIMARY OPEN ANGLE GLAUCOMA OR OCULAR HYPERTENSION

Conditions
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Primary Open-Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: PF-04217329 - Lowest Dose
* Drug: PF-04217329 - Low Dose
* Drug: PF-04217329 - Middle Dose
* Drug: PF-04217329 - High Middle Dose
* Drug: PF-04217329 - High Dose
* Drug: PF-4217329 - Highest Dose
* Drug: PF-04217329 - Vehicle
* Drug: Latanoprost Vehicle
* Drug: PF-04217329 - Low Dose
* Drug: Latanoprost Vehicle
* Drug: PF-04217329 - Middle Dose
* Drug: Latanoprost Vehicle
* Drug: PF-04217329 - High Dose
* Drug: Latanoprost 0.005%
* Drug: PF-04217329 - Low Dose
* Drug: Latanoprost 0.005%
* Drug: PF-04217329 - Middle Dose
* Drug: Latanoprost 0.005%
* Drug: PF-04217329 - High Dose
* Drug: Latanoprost 0.005%
* Drug: PF-04217329 - Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary open-angle glaucoma (including pigmentary or pseudoexfoliative) or ocular hypertension in 1 or both eyes. Qualifying intraocular pressure (IOP) in the same eye at the Eligibility 1 and 2 measurements. Exclusion Criteria: Closed/barely open anterior chamber angle or a history of acute angle closure in either eye. Anticipate the need to initiate or modify medication (systemic or topical) that is known to affect intraocular pressure (IOP) during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1: PF-04217329 - Lowest Dose<br> | Drug: PF-04217329 - Lowest Dose<br>* 1 drop of lowest dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 1: PF-04217329 - Low Dose<br> | Drug: PF-04217329 - Low Dose<br>* 1 drop of low dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 1: PF-04217329 - Middle Dose<br> | Drug: PF-04217329 - Middle Dose<br>* 1 drop of middle dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 1: PF-04217329 - High Middle Dose<br> | Drug: PF-04217329 - High Middle Dose<br>* 1 drop of high middle dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 1: PF-04217329 - High Dose<br> | Drug: PF-04217329 - High Dose<br>* 1 drop of high dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 1: PF-02417329 - Highest Dose<br> | Drug: PF-4217329 - Highest Dose<br>* 1 drop of highest dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 1: PF-04217329 - Vehicle<br> | Drug: PF-04217329 - Vehicle<br>* 1 drop of PF-04217329 vehicle, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 2: PF-04217329 - Low Dose + Latanoprost Vehicle<br> | Drug: Latanoprost Vehicle<br>* 1 drop of latanoprost vehicle, once a day, per dosed eye for duration of study.<br>Drug: PF-04217329 - Low Dose<br>* Five minutes after latanoprost vehicle, 1 drop of low dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 2: PF-04217329 - Middle Dose + Latanoprost Vehicle<br> | Drug: Latanoprost Vehicle<br>* 1 drop of latanoprost vehicle, once a day, per dosed eye for duration of study.<br>Drug: PF-04217329 - Middle Dose<br>* Five minutes after latanoprost vehicle, 1 drop of middle dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 2: PF-04217329 - High Dose + Latanoprost Vehicle<br> | Drug: Latanoprost Vehicle<br>* 1 drop of latanoprost vehicle, once a day, per dosed eye for duration of study.<br>Drug: PF-04217329 - High Dose<br>* Five minutes after latanoprost vehicle, 1 drop of high dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 2: PF-04217329 - Low Dose + Latanoprost 0.005%<br> | Drug: Latanoprost 0.005%<br>* 1 drop of latanoprost 0.005%, once a day, per dosed eye for duration of study.<br>Drug: PF-04217329 - Low Dose<br>* Five minutes after latanoprost 0.005%, 1 drop of low dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 2: PF-04217329 - Middle Dose + Latanoprost 0.005%<br> | Drug: Latanoprost 0.005%<br>* 1 drop of latanoprost 0.005%, once a day, per dosed eye for duration of study.<br>Drug: PF-04217329 - Middle Dose<br>* Five minutes after latanoprost 0.005%, 1 drop middle dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 2: PF-04217329 - High Dose + Latanoprost 0.005%<br> | Drug: Latanoprost 0.005%<br>* 1 drop of latanoprost 0.005%, once a day, per dosed eye for duration of study.<br>Drug: PF-04217329 - High Dose<br>* Five minutes after latanoprost 0.005%, 1 drop high dose PF-04217329, once a day, per dosed eye for duration of study.<br>|
| Experimental: Stage 2: PF-04217329 - Vehicle + Latanoprost 0.005%<br> | Drug: Latanoprost 0.005%<br>* 1 drop of latanoprost 0.005%, once a day, per dosed eye for duration of study.<br>Drug: PF-04217329 - Vehicle<br>* Five minutes after latanoprost 0.005%, 1 drop of PF-04217329 vehicle, once a day, per dosed eye for duration of study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Diurnal Intra Ocular Pressure (IOP) in Study Eye at Day 14: Stage I | Diurnal IOP was defined as the mean IOP over 24 hours. IOP was measured using Goldmann applanation tonometer. IOP was measured in both the eyes, and the eye with higher IOP reading at the 2 eligibility visits was referred as 'study eye' for efficacy assessment. If both the measurements were equal, right eye was selected as the study eye. IOP was measured twice in the same eye, and if the difference between 2 measurements was less than or equal to 2 millimeter of mercury (mmHg), the mean of the 2 readings was recorded as the IOP at that time point. If the difference between 2 readings was greater than 2 mmHg, a third consecutive reading was taken and the median IOP was recorded as the IOP at that time point. Mean IOP was reported as the average of individual participants' mean or median IOP values. Change from baseline = diurnal IOP at baseline - diurnal IOP at Day 14. | Stage I: Baseline, Day 14 | 
| Change From Baseline in Mean Diurnal Intra Ocular Pressure (IOP) in Study Eye at Day 28: Stage II | Diurnal IOP was defined as the mean IOP over 24 hours. IOP was measured using Goldmann applanation tonometer. IOP was measured in both the eyes, and the eye with higher IOP reading at the 2 eligibility visits was referred as 'study eye' for efficacy assessment. If both the measurements were equal, right eye was selected as the study eye. IOP was measured twice in the same eye, and if the difference between 2 measurements was less than or equal to 2 mmHg, the mean of the 2 readings was recorded as the IOP at that time point. If the difference between 2 readings was greater than 2 mmHg, a third consecutive reading was taken and the median IOP was recorded as the IOP at that time point. Mean IOP was reported as the average of individual participants' mean or median IOP values. Change from baseline = diurnal IOP at baseline - diurnal IOP at Day 28. | Stage II: Baseline, Day 28 | 
| Number of Participants With Treatment Emergent Ocular Adverse Events (AEs): Stage I | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study medication and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Ocular AEs were the events which were localized in the ocular region. | Stage I: Day 1 up to 28 days after last dose of study medication (up to 44 days) | 
| Number of Participants With Treatment Emergent Ocular Adverse Events (AEs): Stage II | An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study medication and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Ocular AEs were the events which were localized in the ocular region. | Stage II: Day 1 up to 28 days after last dose of study medication (up to 59 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Intra Ocular Pressure (IOP) in Study Eye: Stage I | IOP was measured using Goldmann applanation tonometer. IOP was measured in both the eyes, and the eye with higher IOP reading at the 2 eligibility visits was referred as 'study eye' for efficacy assessment. If both the measurements were equal, right eye was selected as the study eye. IOP was measured twice in the same eye, and if the difference between 2 measurements was less than or equal to 2 mmHg, the mean of the 2 readings was recorded as the IOP at that time point. If the difference between 2 readings was greater than 2 mmHg, a third consecutive reading was taken and the median IOP was recorded as the IOP at that time point. Mean IOP was reported as the average of individual participants' mean or median IOP values. | Stage I: 8 ante meridiem (AM) on Day 1, 8 AM, 10 AM, 1 post meridiem (PM), 4 PM on Day 7, and 14 | 
| Change From Baseline in Mean Intra Ocular Pressure (IOP) in Study Eye at Day 1 (8 AM), 7 and 14 (8 AM, 10 AM, 1 PM, 4 PM): Stage I | IOP was measured using Goldmann applanation tonometer. IOP was measured in both eyes, and the eye with higher IOP reading at 2 eligibility visits was referred as 'study eye' for efficacy assessment. If both measurements were equal, right eye was selected as the study eye. IOP was measured twice in the same eye, and if the difference between 2 measurements was less than or equal to 2 mmHg, the mean of the 2 readings was recorded as the IOP at that time point. If the difference between 2 readings was greater than 2 mmHg, a third consecutive reading was taken and the median IOP was recorded as the IOP at that time point. Mean IOP was reported as the average of individual participants' mean or median IOP values. Change from baseline = baseline IOP - post-baseline IOP. Change at various post-dose time points was calculated from the baseline values at same time points on Day 0 (for example, value at 8 AM on Day 0 was used as baseline value for 8 AM value on Day 1, 7 and 14). | Stage I: 8 AM, 10 AM, 1 PM, 4 PM on Day 0 (Baseline), 8 AM on Day 1, 8 AM, 10 AM, 1 PM, 4 PM on Day 7, and 14 | 
| Mean Intra Ocular Pressure (IOP) in Study Eye: Stage II | IOP was measured using Goldmann applanation tonometer. IOP was measured in both the eyes, and the eye with higher IOP reading at the 2 eligibility visits was referred as 'study eye' for efficacy assessment. If both the measurements were equal, right eye was selected as the study eye. IOP was measured twice in the same eye, and if the difference between 2 measurements was less than or equal to 2 mmHg, the mean of the 2 readings was recorded as the IOP at that time point. If the difference between 2 readings was greater than 2 mmHg, a third consecutive reading was taken and the median IOP was recorded as the IOP at that time point. Mean IOP was reported as the average of individual participants' mean or median IOP values. | Stage II: 8 AM on Day 1; 8 AM, 10 AM, 1 PM, 4 PM on Days 7, 14, and 28 | 
| Change From Baseline in Mean Intra Ocular Pressure (IOP) in Study Eye at Day 1 (8 AM), 7 (8 AM, 10 AM, 1 PM, 4 PM), 14 (8 AM, 10 AM, 1 PM, 4 PM) and Day 28 (8 AM, 10 AM, 1 PM, 4 PM): Stage II | IOP was measured using Goldmann applanation tonometer. IOP was measured in both eyes, and the eye with higher IOP reading at 2 eligibility visits was referred as 'study eye' for efficacy assessment. If both measurements were equal, right eye was selected as the study eye. IOP was measured twice in the same eye, and if the difference between 2 measurements was less than or equal to 2 mmHg, the mean of the 2 readings was recorded as the IOP at that time point. If the difference between 2 readings was greater than 2 mmHg, a third consecutive reading was taken and the median IOP was recorded as the IOP at that time point. Mean IOP was reported as the average of individual participants' mean or median IOP values. Change from baseline = baseline IOP - post-baseline IOP. Change at various post-dose time points was calculated from the baseline values at same time points on Day 0 (for example, value at 8 AM on Day 0 was used as baseline value for 8 AM value on Day 1, 7, 14 and 28). | Stage II: 8 AM, 10 AM, 1 PM, and 4 PM on Day 0 (Baseline), 8 AM on Day 1; 8 AM, 10 AM, 1 PM, 4 PM on Days 7, 14, and 28 | 
| Percentage of Participants Reaching and Maintaining Target Intra Ocular Pressure (IOP): Stage I | Percentage of participants who reached an IOP of less than or equal to (<=) 18 mmHg by post-eligibility visit (Day 1) and maintained an IOP <= 18 mm Hg across all post-eligibility visits in Stage I were reported. IOP was measured using Goldmann applanation tonometer. | Stage I: Day 1 up to Day 14 | 
| Percentage of Participants Reaching and Maintaining Target Intra Ocular Pressure (IOP): Stage II | Percentage of participants who reached an IOP <= 18 mmHg by post-eligibility visit (Day 1) and maintained an IOP <= 18 mm Hg across all post-eligibility visits in Stage II were reported. IOP was measured using Goldmann applanation tonometer. | Stage II: Day 1 up to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open-Angle Glaucoma, Ocular Hypertension