PF-06372865 in Subjects With Photosensitive Epilepsy

Study Overview
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Brief Summary
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PF-06372865 in subjects with photosensitive epilepsy

Official Title
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A Double Blind, Randomized, Cross- Over Study Examining Efficacy Of Pf-06372865 In A Photosensitivity Epilepsy Study Using Lorazepam As A Positive Control

Conditions
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Reflex Epilepsy, Photosensitive

Intervention / Treatment
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* Drug: PF-06372865
* Drug: Placebo
* Drug: Lorazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis and history of photoparoxysmal response on electroencephalogram (EEG) with or without a diagnosis of epilepsy for which subjects are taking up to 0 - 2 concomitant antiepileptic drugs. Subjects currently taking antiepileptic drug(s) to be on a stable dose for 4 weeks prior to Screening Visit. A minimum average standardized photosensitive range (SPR) across all screening timepoints of 4 in the most sensitive eye condition and a non-zero average in at least one other eye condition. Exclusion Criteria: Subjects with a history of status epilepticus. Subjects who have experienced a generalized tonic-clonic convulsion in the past 6 months, at the time of the initial screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06372865 dose level 1<br>17.5 milligram (mg) single dose | Drug: PF-06372865<br>* Single dose<br>|
| Experimental: PF-06372865 dose level 2<br>52.5 mg single dose | Drug: PF-06372865<br>* Single dose<br>|
| Placebo Comparator: Placebo<br>Single dose | Drug: Placebo<br>* Placebo for PF-06372865 and placebo for lorazepam<br>|
| Active Comparator: Lorazepam<br>2mg single dose | Drug: Lorazepam<br>* 2 mg single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Standardized Photosensitivity Range (SPR) in the Subject's Most Sensitive Eye Condition | The SPR was defined as the number of frequency steps between and including the lower and upper bound at which a generalized electroencephalogram (EEG) epileptiform activity had occurred, whereby subjects were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The SPR is then an integer score that ranges from 0 to 14 with lower scores representing better outcomes. The primary outcome measure was based on the average Least Squares Mean (LSmean) effect over the first 6 hours postdose. | Pre-dose, 1, 2, 4 and 6 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The SPR in the Eye Closure, Eyes Closed, and Eyes Open Condition | The SPR was defined as the number of frequency steps between and including the lower and upper bound at which a generalized electroencephalogram (EEG) epileptiform activity had occurred, whereby subjects were exposed to 14 different frequencies ranging from 2 to 60 flashes per second. The SPR is then an integer score that ranges from 0 to 14 with lower scores representing better outcomes. The outcome measure was based on the average Least Squares Mean (LSmean) effect over the first 6 hours postdose. | Pre-dose, 1, 2, 4 and 6 hours post-dose | 
| The Percentage of Participants With Complete Suppression, Partial Response, and no Response to Intermittent Photic Stimulation (IPS) | Complete suppression: SPR = 0 in all three eye conditions at the same time point. Partial response: A reduction in SPR of at least 3 units from baseline for at least 3 time points, and no time points with at least 3 units of increase, in the most sensitive eye condition; without meeting the complete suppression definition. No response: Did not meet complete suppression or partial response definitions. | Pre-dose, 1, 2, 4 and 6 hours post-dose | 
| Maximum Plasma Concentration (Cmax) of PF-06372865 |  | 1, 2, 4 and 6 hours post-dose | 
| Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06372865 |  | Pre-dose, 1, 2, 3, 4 and 6 hours post-dose | 
| Time for Cmax (Tmax) of PF-06372865 |  | 1, 2, 4 and 6 hours post-dose | 
| Plasma Concentration of Lorazepam |  | 1, 2, 3, 4 and 6 hours post-dose | 
| Number of Participants With Clinically Significant Laboratory Test Abnormalities | Safety laboratory tests included hematological, clinical chemistry (serum) and urinalysis safety tests. | 17 weeks | 
| Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate |  | 17 weeks | 
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings |  | 17 weeks | 
| Number of Participants With Treatment-emergent Adverse Events (AEs) | The all causalities treatment-emergent AEs by System Organ Class and Preferred Term in >5% of subjects. AEs included serious AEs and non-serious AEs. | 19 weeks |