Trial Outcomes & Findings for PF-06372865 in Subjects With Photosensitive Epilepsy (NCT NCT02564029)
NCT ID: NCT02564029
Last Updated: 2018-03-14
Results Overview
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.
COMPLETED
PHASE2
7 participants
Pre-dose, 1, 2, 4 and 6 hours post-dose
2018-03-14
Participant Flow
Participant milestones
| Measure |
All Study Participants
Subjects were randomly allocated to one of 4 different treatment sequences that each included the 4 treatment groups: Placebo, PF-06372865 17.5 mg, PF-06372865 52.5 mg and Lorazepam 2 mg.
|
|---|---|
|
Overall Study
STARTED
|
7
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PF-06372865 in Subjects With Photosensitive Epilepsy
Baseline characteristics by cohort
| Measure |
All Participants
n=7 Participants
A total of 7 participants were enrolled and assigned to study treatment.
|
|---|---|
|
Age, Continuous
|
27 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 1, 2, 4 and 6 hours post-dosePopulation: Full analysis set: all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 primary efficacy measurement in at least 1 study treatment period.
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.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 Participants
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
The Standardized Photosensitivity Range (SPR) in the Subject's Most Sensitive Eye Condition
|
0.57 Units on a scale
Standard Error 0.98
|
1.38 Units on a scale
Standard Error 0.96
|
1.58 Units on a scale
Standard Error 0.97
|
6.80 Units on a scale
Standard Error 0.96
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4 and 6 hours post-dosePopulation: Full analysis set: all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 primary efficacy measurement in at least 1 study treatment period.
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.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 Participants
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
The SPR in the Eye Closure, Eyes Closed, and Eyes Open Condition
Eye Closure
|
0.57 Units on a scale
Standard Error 0.98
|
1.38 Units on a scale
Standard Error 0.96
|
1.58 Units on a scale
Standard Error 0.97
|
6.80 Units on a scale
Standard Error 0.96
|
|
The SPR in the Eye Closure, Eyes Closed, and Eyes Open Condition
Eyes Closed
|
0.33 Units on a scale
Standard Error 0.57
|
0.40 Units on a scale
Standard Error 0.57
|
1.09 Units on a scale
Standard Error 0.57
|
6.84 Units on a scale
Standard Error 0.64
|
|
The SPR in the Eye Closure, Eyes Closed, and Eyes Open Condition
Eyes Open
|
0.04 Units on a scale
Standard Error 0.46
|
0.09 Units on a scale
Standard Error 0.46
|
0.08 Units on a scale
Standard Error 0.46
|
4.46 Units on a scale
Standard Error 0.51
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4 and 6 hours post-dosePopulation: Full analysis set: all participants randomized and who had received at least 1 dose of randomized treatment and had at least 1 primary efficacy measurement in at least 1 study treatment period.
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.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 Participants
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
The Percentage of Participants With Complete Suppression, Partial Response, and no Response to Intermittent Photic Stimulation (IPS)
Complete suppression
|
85.7 Percentage of participants
|
85.7 Percentage of participants
|
85.7 Percentage of participants
|
28.6 Percentage of participants
|
|
The Percentage of Participants With Complete Suppression, Partial Response, and no Response to Intermittent Photic Stimulation (IPS)
Partial response
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
|
The Percentage of Participants With Complete Suppression, Partial Response, and no Response to Intermittent Photic Stimulation (IPS)
No response
|
14.3 Percentage of participants
|
14.3 Percentage of participants
|
14.3 Percentage of participants
|
71.4 Percentage of participants
|
SECONDARY outcome
Timeframe: 1, 2, 4 and 6 hours post-dosePopulation: All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of PF-06372865
|
81.30 ng/mL
Geometric Coefficient of Variation 23
|
200.6 ng/mL
Geometric Coefficient of Variation 45
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 3, 4 and 6 hours post-dosePopulation: All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06372865
|
331.3 ng*hr/mL
Geometric Coefficient of Variation 22
|
771.4 ng*hr/mL
Geometric Coefficient of Variation 56
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 2, 4 and 6 hours post-dosePopulation: All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Time for Cmax (Tmax) of PF-06372865
|
2.12 hour
Full Range 22 • Interval 1.02 to 3.03
|
3.02 hour
Full Range 56 • Interval 1.98 to 5.95
|
—
|
—
|
SECONDARY outcome
Timeframe: 1, 2, 3, 4 and 6 hours post-dosePopulation: All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Plasma Concentration of Lorazepam
1 hours post dose
|
7.38 ng/mL
Standard Deviation 5.92
|
—
|
—
|
—
|
|
Plasma Concentration of Lorazepam
2 hours post dose
|
13.32 ng/mL
Standard Deviation 6.67
|
—
|
—
|
—
|
|
Plasma Concentration of Lorazepam
3 hours post dose
|
17.10 ng/mL
Standard Deviation 4.32
|
—
|
—
|
—
|
|
Plasma Concentration of Lorazepam
4 hours post dose
|
17.87 ng/mL
Standard Deviation 2.97
|
—
|
—
|
—
|
|
Plasma Concentration of Lorazepam
6 hours post dose
|
15.93 ng/mL
Standard Deviation 1.92
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 17 weeksPopulation: The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period.
Safety laboratory tests included hematological, clinical chemistry (serum) and urinalysis safety tests.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 Participants
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Laboratory Test Abnormalities
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 17 weeksPopulation: The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 Participants
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 17 weeksPopulation: The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 Participants
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 19 weeksPopulation: The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period.
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.
Outcome measures
| Measure |
PF-06372865 17.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 Participants
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
Placebo
n=7 Participants
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (AEs)
Treatment-emergent non serious AEs
|
4 Participants
|
6 Participants
|
6 Participants
|
5 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (AEs)
Treatment-emergent serious AEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Placebo
PF-06372865 17.5 mg
PF-06372865 52.5 mg
Lorazepam 2 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=7 participants at risk
One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets.
|
PF-06372865 17.5 mg
n=7 participants at risk
One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets.
|
PF-06372865 52.5 mg
n=7 participants at risk
One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets.
|
Lorazepam 2 mg
n=7 participants at risk
One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets.
|
|---|---|---|---|---|
|
Eye disorders
Vision blurred
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Gastrointestinal disorders
Nausea
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
1/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
General disorders
Fatigue
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
|
General disorders
Feeling hot
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
General disorders
Pain
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Nervous system disorders
Disturbance in attention
|
14.3%
1/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/7 • 19 weeks
|
42.9%
3/7 • 19 weeks
|
42.9%
3/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Nervous system disorders
Lethargy
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Nervous system disorders
Somnolence
|
42.9%
3/7 • 19 weeks
|
42.9%
3/7 • 19 weeks
|
57.1%
4/7 • 19 weeks
|
42.9%
3/7 • 19 weeks
|
|
Psychiatric disorders
Euphoric mood
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
|
Psychiatric disorders
Irritability
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
14.3%
1/7 • 19 weeks
|
0.00%
0/7 • 19 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER