PF-06372865 in Subjects With Photosensitive Epilepsy
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02564029
Collaborator
(none)
7
16
4
13.8
0.4
0
Study Details
Study Description
Brief Summary
PF-06372865 in subjects with photosensitive epilepsy
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
7 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
A Double Blind, Randomized, Cross- Over Study Examining Efficacy Of Pf-06372865 In A Photosensitivity Epilepsy Study Using Lorazepam As A Positive Control
Actual Study Start Date
:
Dec 16, 2015
Actual Primary Completion Date
:
Jan 10, 2017
Actual Study Completion Date
:
Feb 7, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PF-06372865 dose level 1 17.5 milligram (mg) single dose |
Drug: PF-06372865
Single dose
|
| Experimental: PF-06372865 dose level 2 52.5 mg single dose |
Drug: PF-06372865
Single dose
|
| Placebo Comparator: Placebo Single dose |
Drug: Placebo
Placebo for PF-06372865 and placebo for lorazepam
|
| Active Comparator: Lorazepam 2mg single dose |
Drug: Lorazepam
2 mg single oral dose
|
Outcome Measures
Primary Outcome Measures
- The Standardized Photosensitivity Range (SPR) in the Subject's Most Sensitive Eye Condition [Pre-dose, 1, 2, 4 and 6 hours post-dose]
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.
Secondary Outcome Measures
- The SPR in the Eye Closure, Eyes Closed, and Eyes Open Condition [Pre-dose, 1, 2, 4 and 6 hours post-dose]
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.
- The Percentage of Participants With Complete Suppression, Partial Response, and no Response to Intermittent Photic Stimulation (IPS) [Pre-dose, 1, 2, 4 and 6 hours post-dose]
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.
- 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 [17 weeks]
Safety laboratory tests included hematological, clinical chemistry (serum) and urinalysis safety tests.
- 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) [19 weeks]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Consultants in Epilepsy & Neurology, PLLC | Boise | Idaho | United States | 83702 |
| 2 | Johns Hopkins University Department of Neurology | Baltimore | Maryland | United States | 21287-7247 |
| 3 | Barnes Jewish Hospital | Saint Louis | Missouri | United States | 63110 |
| 4 | Center for Advanced Medicine | Saint Louis | Missouri | United States | 63110 |
| 5 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 6 | New York University Comprehensive Epilepsy Center | New York | New York | United States | 10016 |
| 7 | Clinical and Translational Research Center | Philadelphia | Pennsylvania | United States | 19104 |
| 8 | Hospital of the Univ of PA Pharmacy Service | Philadelphia | Pennsylvania | United States | 19104 |
| 9 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 10 | Thomas Jefferson University Comprehensive Epilepsy Center | Philadelphia | Pennsylvania | United States | 19107 |
| 11 | Thomas Jefferson University Hospital EEG lab | Philadelphia | Pennsylvania | United States | 19107 |
| 12 | Thomas Jefferson University Investigational Drug Service | Philadelphia | Pennsylvania | United States | 19107 |
| 13 | General Clinical Research Center (GCRC) | Nashville | Tennessee | United States | 37232 |
| 14 | Vanderbilt University Epilepsy Clinic | Nashville | Tennessee | United States | 37232 |
| 15 | Vanderbilt University Hospital Pharmacy | Nashville | Tennessee | United States | 37232 |
| 16 | VU Department of Neurology | Nashville | Tennessee | United States | 37232 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02564029
Other Study ID Numbers:
- B7431005
First Posted:
Sep 30, 2015
Last Update Posted:
Mar 14, 2018
Last Verified:
Feb 1, 2018
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | All Study Participants |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 7 |
| COMPLETED | 7 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | A total of 7 participants were enrolled and assigned to study treatment. |
| Overall Participants | 7 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
27
(7.3)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
5
71.4%
|
| Male |
2
28.6%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
7
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | The Standardized Photosensitivity Range (SPR) in the Subject's Most Sensitive Eye Condition |
|---|---|
| Description | 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. |
| Time Frame | Pre-dose, 1, 2, 4 and 6 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 | 7 | 7 | 7 |
| Least Squares Mean (Standard Error) [Units on a scale] |
0.57
(0.98)
|
1.38
(0.96)
|
1.58
(0.97)
|
6.80
(0.96)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Placebo |
|---|---|---|
| Comments | A mixed effects model was applied with fixed effects for period, time, treatment, and the interaction between treatment and time. Baseline was included as 2 separate covariates. The interaction between each baseline covariate and time were included as fixed effects. Participant was fitted as a random effect and time was fitted as a repeated effect within each participant × period. An unstructured correlation matrix was used. The effect reported is an average across all post-dose measurements. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.23 | |
| Confidence Interval |
(2-Sided) 90% -8.60 to -3.86 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.37 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Placebo |
|---|---|---|
| Comments | A mixed effects model was applied with fixed effects for period, time, treatment, and the interaction between treatment and time. Baseline was included as 2 separate covariates. The interaction between each baseline covariate and time were included as fixed effects. Participant was fitted as a random effect and time was fitted as a repeated effect within each participant × period. An unstructured correlation matrix was used. The effect reported is an average across all post-dose measurements. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.42 | |
| Confidence Interval |
(2-Sided) 90% -7.78 to -3.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Lorazepam 2 mg, Placebo |
|---|---|---|
| Comments | A mixed effects model was applied with fixed effects for period, time, treatment, and the interaction between treatment and time. Baseline was included as 2 separate covariates. The interaction between each baseline covariate and time were included as fixed effects. Participant was fitted as a random effect and time was fitted as a repeated effect within each participant × period. An unstructured correlation matrix was used. The effect reported is an average across all post-dose measurements. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.22 | |
| Confidence Interval |
(2-Sided) 90% -7.60 to -2.84 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.37 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, PF-06372865 52.5 mg |
|---|---|---|
| Comments | A mixed effects model was applied with fixed effects for period, time, treatment, and the interaction between treatment and time. Baseline was included as 2 separate covariates. The interaction between each baseline covariate and time were included as fixed effects. Participant was fitted as a random effect and time was fitted as a repeated effect within each participant × period. An unstructured correlation matrix was used. The effect reported is an average across all post-dose measurements. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.81 | |
| Confidence Interval |
(2-Sided) 90% -1.58 to 3.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.38 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | A mixed effects model was applied with fixed effects for period, time, treatment, and the interaction between treatment and time. Baseline was included as 2 separate covariates. The interaction between each baseline covariate and time were included as fixed effects. Participant was fitted as a random effect and time was fitted as a repeated effect within each participant × period. An unstructured correlation matrix was used. The effect reported is an average across all post-dose measurements. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.01 | |
| Confidence Interval |
(2-Sided) 90% -3.43 to 1.41 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | A mixed effects model was applied with fixed effects for period, time, treatment, and the interaction between treatment and time. Baseline was included as 2 separate covariates. The interaction between each baseline covariate and time were included as fixed effects. Participant was fitted as a random effect and time was fitted as a repeated effect within each participant × period. An unstructured correlation matrix was used. The effect reported is an average across all post-dose measurements. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 90% -2.56 to 2.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | ||
| Title | The SPR in the Eye Closure, Eyes Closed, and Eyes Open Condition |
|---|---|
| Description | 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. |
| Time Frame | Pre-dose, 1, 2, 4 and 6 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 | 7 | 7 | 7 |
| Eye Closure |
0.57
(0.98)
|
1.38
(0.96)
|
1.58
(0.97)
|
6.80
(0.96)
|
| Eyes Closed |
0.33
(0.57)
|
0.40
(0.57)
|
1.09
(0.57)
|
6.84
(0.64)
|
| Eyes Open |
0.04
(0.46)
|
0.09
(0.46)
|
0.08
(0.46)
|
4.46
(0.51)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Placebo |
|---|---|---|
| Comments | In eye closure condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.23 | |
| Confidence Interval |
(2-Sided) 90% -8.60 to -3.86 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.37 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Placebo |
|---|---|---|
| Comments | In eye closure condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.42 | |
| Confidence Interval |
(2-Sided) 90% -7.78 to -3.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Lorazepam 2 mg, Placebo |
|---|---|---|
| Comments | In eye closure condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.22 | |
| Confidence Interval |
(2-Sided) 90% -7.60 to -2.84 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.37 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, PF-06372865 52.5 mg |
|---|---|---|
| Comments | In eye closure condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.81 | |
| Confidence Interval |
(2-Sided) 90% -1.58 to 3.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.38 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | In eye closure condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.01 | |
| Confidence Interval |
(2-Sided) 90% -3.43 to 1.41 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | In eye closure condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 90% -2.56 to 2.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Placebo |
|---|---|---|
| Comments | In eyes closed condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.51 | |
| Confidence Interval |
(2-Sided) 90% -8.01 to -5.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.79 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Placebo |
|---|---|---|
| Comments | In eyes closed condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.44 | |
| Confidence Interval |
(2-Sided) 90% -7.93 to -4.95 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.78 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Lorazepam 2 mg, Placebo |
|---|---|---|
| Comments | In eyes closed condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.74 | |
| Confidence Interval |
(2-Sided) 90% -7.20 to -4.28 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.76 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, PF-06372865 52.5 mg |
|---|---|---|
| Comments | In eyes closed condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.07 | |
| Confidence Interval |
(2-Sided) 90% -1.31 to 1.46 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | In eyes closed condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.77 | |
| Confidence Interval |
(2-Sided) 90% -2.19 to 0.65 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | In eyes closed condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 90% -2.09 to 0.70 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Placebo |
|---|---|---|
| Comments | In eyes open condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.42 | |
| Confidence Interval |
(2-Sided) 90% -5.60 to -3.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Placebo |
|---|---|---|
| Comments | In eyes open condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.37 | |
| Confidence Interval |
(2-Sided) 90% -5.57 to -3.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Lorazepam 2 mg, Placebo |
|---|---|---|
| Comments | In eyes open condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.38 | |
| Confidence Interval |
(2-Sided) 90% -5.57 to -3.19 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, PF-06372865 52.5 mg |
|---|---|---|
| Comments | In eyes open condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 90% -1.08 to 1.19 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 17.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | In eyes open condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 90% -1.18 to 1.10 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | PF-06372865 52.5 mg, Lorazepam 2 mg |
|---|---|---|
| Comments | In eyes open condition. The same mixed model repeated measures analysis as applied to the primary outcome measure was used. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 90% -1.11 to 1.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | ||
| Title | The Percentage of Participants With Complete Suppression, Partial Response, and no Response to Intermittent Photic Stimulation (IPS) |
|---|---|
| Description | 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. |
| Time Frame | Pre-dose, 1, 2, 4 and 6 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 | 7 | 7 | 7 |
| Complete suppression |
85.7
1224.3%
|
85.7
NaN
|
85.7
NaN
|
28.6
NaN
|
| Partial response |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| No response |
14.3
204.3%
|
14.3
NaN
|
14.3
NaN
|
71.4
NaN
|
| Title | Maximum Plasma Concentration (Cmax) of PF-06372865 |
|---|---|
| Description | |
| Time Frame | 1, 2, 4 and 6 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg |
|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. |
| Measure Participants | 7 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
81.30
(23)
|
200.6
(45)
|
| Title | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06372865 |
|---|---|
| Description | |
| Time Frame | Pre-dose, 1, 2, 3, 4 and 6 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg |
|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. |
| Measure Participants | 7 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL] |
331.3
(22)
|
771.4
(56)
|
| Title | Time for Cmax (Tmax) of PF-06372865 |
|---|---|
| Description | |
| Time Frame | 1, 2, 4 and 6 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg |
|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. |
| Measure Participants | 7 | 7 |
| Median (Full Range) [hour] |
2.12
(22)
|
3.02
(56)
|
| Title | Plasma Concentration of Lorazepam |
|---|---|
| Description | |
| Time Frame | 1, 2, 3, 4 and 6 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants treated who had at least 1 measureable concentration in the respective study dose period. |
| Arm/Group Title | Lorazepam 2 mg |
|---|---|
| Arm/Group Description | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 |
| 1 hours post dose |
7.38
(5.92)
|
| 2 hours post dose |
13.32
(6.67)
|
| 3 hours post dose |
17.10
(4.32)
|
| 4 hours post dose |
17.87
(2.97)
|
| 6 hours post dose |
15.93
(1.92)
|
| Title | Number of Participants With Clinically Significant Laboratory Test Abnormalities |
|---|---|
| Description | Safety laboratory tests included hematological, clinical chemistry (serum) and urinalysis safety tests. |
| Time Frame | 17 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 | 7 | 7 | 7 |
| Number [Participants] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate |
|---|---|
| Description | |
| Time Frame | 17 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 | 7 | 7 | 7 |
| Number [Participants] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings |
|---|---|
| Description | |
| Time Frame | 17 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 | 7 | 7 | 7 |
| Number [Participants] |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Treatment-emergent Adverse Events (AEs) |
|---|---|
| Description | 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. |
| Time Frame | 19 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who received at least 1 dose of investigational product in the respective study treatment period. |
| Arm/Group Title | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. |
| Measure Participants | 7 | 7 | 7 | 7 |
| Treatment-emergent non serious AEs |
4
57.1%
|
6
NaN
|
6
NaN
|
5
NaN
|
| Treatment-emergent serious AEs |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
Adverse Events
| Time Frame | 19 weeks | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Placebo | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | ||||
| Arm/Group Description | One (1) lorazepam placebo tablet and seven (7) PF-06372865 placebo tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 2.5 mg tablets. | One (1) lorazepam placebo tablet and seven (7) PF-06372865 7.5 mg tablets. | One (1) lorazepam 2 mg tablet and seven (7) PF-06372865 placebo tablets. | ||||
All Cause Mortality |
||||||||
| Placebo | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | PF-06372865 17.5 mg | PF-06372865 52.5 mg | Lorazepam 2 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/7 (57.1%) | 6/7 (85.7%) | 6/7 (85.7%) | 5/7 (71.4%) | ||||
| Eye disorders | ||||||||
| Vision blurred | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain upper | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | ||||
| Nausea | 1/7 (14.3%) | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Vomiting | 1/7 (14.3%) | 1/7 (14.3%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| General disorders | ||||||||
| Fatigue | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||
| Feeling hot | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | ||||
| Pain | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Infections and infestations | ||||||||
| Pharyngitis | 0/7 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Upper respiratory tract infection | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscular weakness | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Nervous system disorders | ||||||||
| Balance disorder | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Disturbance in attention | 1/7 (14.3%) | 1/7 (14.3%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Dizziness | 0/7 (0%) | 3/7 (42.9%) | 3/7 (42.9%) | 1/7 (14.3%) | ||||
| Dysarthria | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | ||||
| Dysgeusia | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | ||||
| Headache | 0/7 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | 0/7 (0%) | ||||
| Lethargy | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | ||||
| Somnolence | 3/7 (42.9%) | 3/7 (42.9%) | 4/7 (57.1%) | 3/7 (42.9%) | ||||
| Psychiatric disorders | ||||||||
| Euphoric mood | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | ||||
| Irritability | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | 0/7 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Oropharyngeal pain | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||
| Rhinorrhoea | 0/7 (0%) | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Rash pruritic | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02564029
Other Study ID Numbers:
- B7431005
First Posted:
Sep 30, 2015
Last Update Posted:
Mar 14, 2018
Last Verified:
Feb 1, 2018