Vision Testing in Patients With Partial Seizures Receiving Either Lyrica or Placebo

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00351611
• Collaborator: (none)
• Enrollment: 187
• Locations: 150
• Arms: 2
• Actual Duration (Months): 162.3
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Patients with partial seizures currently taking 1-3 antiepileptic medications will have a 50:50 chance to receive Lyrica 300 mg per day or placebo (no active ingredients) added on to their current medications for 3 months. Neither the study doctor nor the patient will know the medication assignment. Vision testing will be performed prior to receiving the study treatment and at the end of the study to see if there are any changes.

Condition or Disease	Intervention/Treatment	Phase
Epilepsies, Partial	Drug: Lyrica (pregabalin); Drug: placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: PROSPECTIVE RANDOMIZED 12-WEEK CONTROLLED STUDY OF VISUAL FIELD CHANGE IN SUBJECTS WITH PARTIAL SEIZURES RECEIVING PREGABALIN OR PLACEBO
• Actual Study Start Date: Jul 26, 2006
• Actual Primary Completion Date: Feb 4, 2020
• Actual Study Completion Date: Feb 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Active drug	Drug: Lyrica (pregabalin); 150 mg twice a day, oral administration
Placebo Comparator: Placebo placebo comparator	Drug: placebo; Twice a day, oral administration

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Decrease (p<0.05) From Baseline in Threshold Value in Any 5 or More Points in Humphrey 24-2 Swedish Interactive Threshold Algorithm (SITA) Standard Testing at Week 12 or Early Termination [Baseline, Week 12 or Early Termination (any time up to Week 12)]

   In this primary outcome measure, percentage of participants is reported, with a decrease in the threshold value from baseline to Week 12 or termination in any 5 or more points (in either eye) at the p<0.05 level repeated in the same 5 points on subsequent computerized automated perimetry testing (Humphrey 24-2 SITA standard). It was derived from the Humphrey 24-2 SITA standard visual field analyzer. For each eye there were 52 test points. For each test point, the Humphrey analyzer determined the threshold value for sensitivity to light by the participant. In addition, for each of the 52 points, the test provided probabilities (p<0.05, p<0.02, etc.) that a participant with normal vision of the same age would have the same result, i.e., that the measured value at that point was at or below the respective percentile of the age-specific empiric distribution at that position of the field for normal participants.

Secondary Outcome Measures

1. Change From Baseline in Mean Deviation Score From Humphrey Threshold Test at Week 12 or Early Termination [Baseline, Week 12 or Early Termination (any time up to Week 12)]

   Mean deviation (MD) is a global index of visual field depression. The MD ranges from 0 decibels (no defect) to about -32 decibels (end-stage damage), higher scores indicate worse condition. It is derived from the Humphrey 24-2 SITA standard visual field analyzer. Change in mean deviation score from baseline to Week 12 or termination was computed for each participant. As planned, for each participant, the worst eye (eye with the greatest decrease in mean deviation) was used in the analysis and data is reported for same.

2. Change From Baseline in Visual Acuity at Week 12 or Early Termination [Baseline, Week 12 or Early Termination (any time up to Week 12)]

   Visual acuity best-corrected (with glasses or best possible glasses prescription) was measured using early treatment diabetic retinopathy study (ETDRS) charts. There were 2 ETDRS charts. The letters on chart A were read using the right eye and on chart B using the left eye. The participants started from the top of the chart to down. The participants read down the chart until they reached a row where a minimum of 3 letters on a line could not be read. The participants were scored by number of letters identified correctly. Range was from 0 to 70, with higher scores indicate better visual acuity. As planned, for each participant, the worst eye (eye with the greatest decrease in visual acuity) was used in the analysis and data is reported for same.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Epilepsy partial seizure subjects.

• Currently taking 1 to 3 antiepileptic drugs.

Exclusion Criteria:

• Pre-existing eye diseases (glaucoma).

• Insufficient response to pregabalin in the treatment of partial seizure, or patients currently receiving pregabalin treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurology Center, P.C.	Mobile	Alabama	United States	36607
2	Premier Medical Group	Mobile	Alabama	United States	36608
3	Neurology Clinic, PC	Northport	Alabama	United States	35476
4	North River Ophthalmology	Tuscaloosa	Alabama	United States	35406
5	Western Neurosurgery	Tucson	Arizona	United States	85710
6	Office of Robert Snyder, MD	Tucson	Arizona	United States	85712
7	REM Medical Clinical Research	Tucson	Arizona	United States	85712
8	NEA Baptist Clinic - Clinical Research Center	Jonesboro	Arkansas	United States	72401
9	NEA Baptist Clinic	Jonesboro	Arkansas	United States	72401
10	NEA Baptst Clinic	Jonesboro	Arkansas	United States	72401
11	Chenal MRI	Little Rock	Arkansas	United States	72205
12	Clinical Trials, Inc.	Little Rock	Arkansas	United States	72205
13	Eye Care Arkansas	Little Rock	Arkansas	United States	72205
14	Radiology Consultants	Little Rock	Arkansas	United States	72205
15	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
16	Barbara Swartz, MD, Inc	Costa Mesa	California	United States	92627
17	Mireille P. Hamparian	Glendale	California	United States	91206
18	Lakeside Vision Center	Irvine	California	United States	92604
19	Eye Treatment Center, Inc.	Long Beach	California	United States	90813
20	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92658
21	Clinical Innovations, Inc.	Paramount	California	United States	90723
22	Yale University School of Medicine	New Haven	Connecticut	United States	06520-8018
23	Bradenton Research Center, Inc	Bradenton	Florida	United States	34205
24	The Eye Associates	Bradenton	Florida	United States	34209
25	SJS Clinical Research, Inc.	Destin	Florida	United States	32541
26	White Wilson Medical Center	Fort Walton Beach	Florida	United States	32547
27	Pharmax Research Clinic, Inc.	Miami	Florida	United States	33126
28	Dr. Raul F. Masvidal, MD, PA	Miami	Florida	United States	33134
29	David M Klein, MD, PA	Port Charlotte	Florida	United States	33948
30	Medsol Clinical Research Center, Inc	Port Charlotte	Florida	United States	33952
31	Intercoastal Medical Research Center	Sarasota	Florida	United States	34232
32	Dr. Nicholas Monsul	Sarasota	Florida	United States	34239
33	Sarasota Retinal Institute	Sarasota	Florida	United States	34239
34	Coastal Research Associates, LLC	Atlanta	Georgia	United States	30339
35	Comprehensive Neurology Specialists, PC	Suwanee	Georgia	United States	30024
36	Professional Research Network of Kansas	Wichita	Kansas	United States	67203
37	Vitreo-Retinal Consultants and Surgeons	Wichita	Kansas	United States	67214
38	Neuromedical Clinic of Central Louisiana	Alexandria	Louisiana	United States	71301
39	Louisiana Eye and Laser Center	Alexandria	Louisiana	United States	71303
40	University of Maryland Eye Associates, P.A.	Baltimore	Maryland	United States	21201
41	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
42	University of Maryland	Baltimore	Maryland	United States	21201
43	Glaucoma Plus Eye Care, LLC	Columbia	Maryland	United States	21044
44	Center for Brain and Neuro Care, LLC	Fulton	Maryland	United States	20759
45	Bergman Eye Associates	Hagerstown	Maryland	United States	21740
46	Neurology Consultant, P.A.	Hagerstown	Maryland	United States	21740
47	The Center for Clinical Research	Hagerstown	Maryland	United States	21740
48	Harper Hospital	Detroit	Michigan	United States	48201
49	Wayne State University	Detroit	Michigan	United States	48201
50	Fraser Eye Care Center	Fraser	Michigan	United States	48026
51	Minneapolis Clinic of Neurology, Ltd	Golden Valley	Minnesota	United States	55422
52	University of Missouri	Columbia	Missouri	United States	65212
53	CCN-MS & Neurology Associates	Columbia	Missouri	United States	65401
54	Nevada Eye Care	Las Vegas	Nevada	United States	89119
55	Neurology Center of Las Vegas	Las Vegas	Nevada	United States	89128
56	Institute of Neurological Care	Englewood Cliffs	New Jersey	United States	07632
57	Office of Patricia Burke, MD	Paramus	New Jersey	United States	07652
58	Dent Neurologic Institute	Amherst	New York	United States	14226
59	Dent Neurosciences Research Center	Amherst	New York	United States	14226
60	Western New York Ophthalmology Group	Amherst	New York	United States	14226
61	Buffalo General Hospital	Buffalo	New York	United States	14203
62	The Jacobs Neurological Institute Comprehensive Epilepsy Center	Buffalo	New York	United States	14209
63	Guilford Neurologic Associates, Inc	Greensboro	North Carolina	United States	27405
64	Digby Eye Associates	Greensboro	North Carolina	United States	27408
65	Clinical Research of Winston-Salem	Winston-Salem	North Carolina	United States	27103
66	Salem Neurological Center, PA	Winston-Salem	North Carolina	United States	27103
67	Office of Dr. James D. Branch, MD	Winston-Salem	North Carolina	United States	27107
68	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
69	The Cleveland Clinic	Cleveland	Ohio	United States	44195
70	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
71	Jeffrey Shaver, MD	Edmond	Oklahoma	United States	73013
72	Sooner Clinical Research	Oklahoma City	Oklahoma	United States	73112
73	Clinical Trials of America, Inc.	Eugene	Oregon	United States	97401
74	Oregon Eye Consultants, LLC	Eugene	Oregon	United States	97401
75	Pacific Women's Center, LLC	Eugene	Oregon	United States	97401
76	Oregon Neurology Associates	Springfield	Oregon	United States	97477
77	Daniel J. Nadler, MD, PC	Beaver	Pennsylvania	United States	15009
78	Heritage Valley Health System	Beaver	Pennsylvania	United States	15009
79	Valley Neurological Associates	Monaca	Pennsylvania	United States	15061
80	Center For Advanced Eye Care	Greenville	South Carolina	United States	29615
81	Premier Neurology, PC	Greer	South Carolina	United States	29650
82	Coastal Carolina Research Center	Mount Pleasant	South Carolina	United States	29464
83	Glaucoma Consultants and Center for Eye Research, PA	Mount Pleasant	South Carolina	United States	29464
84	Tidewater Neurology	Mount Pleasant	South Carolina	United States	29464
85	Neurology Centers of the Carolinas	Spartanburg	South Carolina	United States	29302
86	Piedmont Eye Associates	Spartanburg	South Carolina	United States	29303
87	Envision Eye Care	Bristol	Tennessee	United States	37620
88	Tri-state Mountain Neurology Associates, PC	Johnson City	Tennessee	United States	37604
89	Semmes Murphey Clinic	Memphis	Tennessee	United States	38104
90	Semmes Murphey Clinic	Memphis	Tennessee	United States	38120
91	University of Tennessee Health Science Center	Memphis	Tennessee	United States	38163
92	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
93	Texan Eye	Austin	Texas	United States	78731
94	Texas Neurology, PA	Dallas	Texas	United States	75214
95	Glaucoma Associates of Texas	Dallas	Texas	United States	75231
96	Egret Bay Neurology, PA	Houston	Texas	United States	77058
97	DeHaven Eye Clinic	Longview	Texas	United States	75601
98	Diagnostic Clinic of Longview Center for Clinical Research	Longview	Texas	United States	75605
99	Diagnostic Clinic of Longview, PA	Longview	Texas	United States	75605
100	Coastal Eye Associates	Webster	Texas	United States	77598
101	Neurological Associates Sarah Cannon Cancer Institute;	Richmond	Virginia	United States	23229
102	Medical College of Wisconsin Department of Neurology Froedtert Memorial Hospital	Milwaukee	Wisconsin	United States	53226-3522
103	Medical College of Wisconsin Eye Institute	Milwaukee	Wisconsin	United States	53226
104	DKC 2	Sofia		Bulgaria	1000
105	Chetvarta nevrologichna klinika	Sofia		Bulgaria	1113
106	Otdelenie po Nevrologia, Vtora MBAL	Sofia		Bulgaria	1202
107	Otdelenie po nevrologia, MBAL "Tokuda Bolnitsa"	Sofia		Bulgaria	1407
108	Universitetska mnogoprofilna bolnitsa za aktivno lechenieAleksandrovska, Klinika po Nevrologia	Sofia		Bulgaria	1431
109	Otdelenie po nervni bolesti, MBAL Doverie	Sofia		Bulgaria	1632
110	Fakultni Thomayerova nemocnice	Praha 4		Czechia	140 59
111	NEUROPS s.r.o.	Rychnov nad Kneznou		Czechia	516 01
112	Ocni ambulance	Rychnov nad Kneznou		Czechia	516 01
113	Synexus Kft.	Budapest		Hungary	1036
114	Budapest Retina Associates Kft.	Budapest		Hungary	1133
115	Orszagos Idegtudomanyi Intezet, Stroke es Epilepszia Osztaly	Budapest		Hungary	1145
116	Orszagos Idegtudomanyi Intezet	Budapest		Hungary	1145
117	Csongrad Megyei Egeszsegugyi Ellato Kozpont Hodmezovasarhely-Mako,	Hodmezovasarhely		Hungary	6800
118	Netra Diagnostics (P) Ltd	Abids, Hyderabad	Andhra Pradesh	India	500 001
119	Krishna Institute of Medical Sciences Ltd.	Secunderabad	Andhra Pradesh	India	500 003
120	King George Hospital	Visakhapatnam	Andhra Pradesh	India	530002
121	M.S. Ramaiah Medical College and Hospitals,	Bangalore,	Karnataka	India	560054
122	St. John's Medical College Hospital	Bangalore	Karnataka	India	560034
123	Mallikatta Neuro Center	Mangalore	Karnataka	India	575002
124	Kasturba Medical College and Hospital,	Manipal	Karnataka	India	576 104
125	Eye Site,	Indore	Madhya Pradesh	India	452 001
126	M.G.M. Medical College & M. Y. Hospitals,	Indore	Madhya Pradesh	India	452 001
127	T.N.M.C and B.Y.L Nair Charitable Hospital,	Mumbai	Maharashtra	India	400 008
128	Kelkar Nursing Home	Pune	Maharashtra	India	411004
129	Sahyadri Clinical Research Development Centre, A unit of Sahyadri Hospitals Ltd,	Pune	Maharashtra	India	411004
130	Sahyadri Speciality Hospital	Pune	Maharashtra	India	411004
131	Vijaya Health Centre	Chennai	Tamil NADU	India	600 026
132	Yashoda Hospital	Hyderabad	Telangana	India	500 082
133	Dr. Ram Manohar Lohia Hospital	New Delhi		India	110 001
134	All India Institute of Medical Sciences (AIIMS)	New Delhi		India	110029
135	Keimyung University Dongsan Hospital	Daegu		Korea, Republic of	41931
136	Seoul National University Hospital	Seoul		Korea, Republic of	03080
137	Yonsei University Health System Severance Hospital	Seoul		Korea, Republic of	03722
138	Asan Medical Center	Seoul		Korea, Republic of	05505
139	Samsung Medical Center	Seoul		Korea, Republic of	06351
140	Instituto Biomedico de Investigacion AC	Aguascalientes	Aquascalientes	Mexico	20127
141	Dr. Ruben Munoz Flores de la Torre Ophthalmic Office	Aquascalientes		Mexico	20000
142	Hospital Central Dr. Ignacio Morones Prieto	San Luis Potosi		Mexico	78240
143	Niepubliczny Zaklad Opieki Zdrowotnej "OKOmed" s.c.	Goczalkowice Zdroj		Poland	43-230
144	NZOZ Tommed	Katowice		Poland	40-662
145	Centrum Medyczne Dendryt	Katowice		Poland	40-683
146	Prywatny Gabinet Psychiatryczny dr Ewa Dereszak-Kozanecka	Krakow		Poland	30-040
147	Prywatny Gabinet Okulistyczny dr. n.med. Teresa Gedliczka	Krakow		Poland	30-319
148	NZOZ Centrum Leczenia Padaczki i Migreny	Krakow		Poland	31-209
149	Khon Kaen University, Faculty of Medicine, Neurology Unit, Department of Medicine	Muang	Khon Kaen	Thailand	40002
150	Phramongkutklao hospital,	Bangkok		Thailand	10400

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Sep 25, 2020
• Statistical Analysis Plan - Sep 30, 2020

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00351611
• Other Study ID Numbers: A0081096; 2009-014269-25
• First Posted: Jul 13, 2006
• Last Update Posted: Apr 13, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: epilepsy partial seizure treatment with pregabalin or placebo; vision testing
• Additional relevant MeSH terms: Epilepsy; Seizures; Epilepsies, Partial; Pregabalin

Study Results

Participant Flow

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants were randomized to receive pregabalin. In Week 1 (titration), participants received pregabalin 150 milligram per day (mg/day) as 75 mg oral capsules twice daily. From Week 2 to 12, participants received pregabalin 300 mg/day as 150 mg oral capsules twice daily. In Week 13 (tapering), participants received 150 mg/day as 75 mg oral capsules twice daily. Participants were followed up from Week 14 to 15. If participants not tolerated 300 mg/day dose, they were discontinued from the study.	Participants were randomized to receive placebo matched to pregabalin from Week 1 to 13 and were followed up from Week 14 to 15.
Period Title: Overall Study
STARTED	89	98
Treated	89	98
COMPLETED	75	88
NOT COMPLETED	14	10

Baseline Characteristics

Arm/Group Title	Pregabalin	Placebo	Total
Arm/Group Description	Participants were randomized to receive pregabalin. In Week 1 (titration), participants received pregabalin 150 mg/day as 75 mg oral capsules twice daily. From Week 2 to 12, participants received pregabalin 300 mg/day as 150 mg oral capsules twice daily. In Week 13 (tapering), participants received 150 mg/day as 75 mg oral capsules twice daily. Participants were followed up from Week 14 to 15. If participants not tolerated 300 mg/day dose, they were discontinued from the study.	Participants were randomized to receive placebo matched to pregabalin from Week 1 to 13 and were followed up from Week 14 to 15.	Total of all reporting groups
Overall Participants	89	98	187
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.1 (12.1)	39.1 (11.6)	38.6 (11.8)
Sex: Female, Male (Count of Participants)
Female	44 49.4%	46 46.9%	90 48.1%
Male	45 50.6%	52 53.1%	97 51.9%
Race/Ethnicity, Customized (Count of Participants)
White	47 52.8%	51 52%	98 52.4%
Black	4 4.5%	5 5.1%	9 4.8%
Asian	34 38.2%	40 40.8%	74 39.6%
Others	4 4.5%	2 2%	6 3.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Decrease (p<0.05) From Baseline in Threshold Value in Any 5 or More Points in Humphrey 24-2 Swedish Interactive Threshold Algorithm (SITA) Standard Testing at Week 12 or Early Termination
Description	In this primary outcome measure, percentage of participants is reported, with a decrease in the threshold value from baseline to Week 12 or termination in any 5 or more points (in either eye) at the p<0.05 level repeated in the same 5 points on subsequent computerized automated perimetry testing (Humphrey 24-2 SITA standard). It was derived from the Humphrey 24-2 SITA standard visual field analyzer. For each eye there were 52 test points. For each test point, the Humphrey analyzer determined the threshold value for sensitivity to light by the participant. In addition, for each of the 52 points, the test provided probabilities (p<0.05, p<0.02, etc.) that a participant with normal vision of the same age would have the same result, i.e., that the measured value at that point was at or below the respective percentile of the age-specific empiric distribution at that position of the field for normal participants.
Time Frame	Baseline, Week 12 or Early Termination (any time up to Week 12)

Outcome Measure Data

Analysis Population Description

Per protocol population included all participants randomized to treatment who received at least 1 dose of study medication and excluded participants who had a decrease in at least 5 points at termination but did not return for a repeat test.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants were randomized to receive pregabalin. In Week 1 (titration), participants received pregabalin 150 mg/day as 75 mg oral capsules twice daily. From Week 2 to 12, participants received pregabalin 300 mg/day as 150 mg oral capsules twice daily. In Week 13 (tapering), participants received 150 mg/day as 75 mg oral capsules twice daily. Participants were followed up from Week 14 to 15. If participants not tolerated 300 mg/day dose, they were discontinued from the study.	Participants were randomized to receive placebo matched to pregabalin from Week 1 to 13 and were followed up from Week 14 to 15.
Measure Participants	78	90
Number [Percentage of participants]	3.8 4.3%	5.6 5.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	A 2-sided 95 percent (%) confidence interval (CI) on the difference in percentage of participants, between pregabalin and placebo was constructed using unconditional exact methods.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the upper CI bound was less than 0.10 (10%).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage of participants
	Estimated Value	-1.7094
	Confidence Interval	(2-Sided) 95%; -9.1751 to 5.9784
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Mean Deviation Score From Humphrey Threshold Test at Week 12 or Early Termination
Description	Mean deviation (MD) is a global index of visual field depression. The MD ranges from 0 decibels (no defect) to about -32 decibels (end-stage damage), higher scores indicate worse condition. It is derived from the Humphrey 24-2 SITA standard visual field analyzer. Change in mean deviation score from baseline to Week 12 or termination was computed for each participant. As planned, for each participant, the worst eye (eye with the greatest decrease in mean deviation) was used in the analysis and data is reported for same.
Time Frame	Baseline, Week 12 or Early Termination (any time up to Week 12)

Outcome Measure Data

Analysis Population Description

ITT population included all participants randomized to treatment, who received at least 1 dose of study medication. Here, "Overall Number of Participants Analyzed" refers to those participants who were evaluable for this outcome measure.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants were randomized to receive pregabalin. In Week 1 (titration), participants received pregabalin 150 mg/day as 75 mg oral capsules twice daily. From Week 2 to 12, participants received pregabalin 300 mg/day as 150 mg oral capsules twice daily. In Week 13 (tapering), participants received 150 mg/day as 75 mg oral capsules twice daily. Participants were followed up from Week 14 to 15. If participants not tolerated 300 mg/day dose, they were discontinued from the study.	Participants were randomized to receive placebo matched to pregabalin from Week 1 to 13 and were followed up from Week 14 to 15.
Measure Participants	83	96
Least Squares Mean (Standard Error) [Decibels]	-0.339 (0.1467)	-0.214 (0.1321)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis of covariance (ANCOVA) with treatment and center in the model and the baseline mean deviation as the covariate was used to construct a 2-sided 95% CI on the difference in least squares (LS) mean between pregabalin and placebo.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority with respect to mean deviation was demonstrated if the lower bound of the CI is greater than -2.0 decibels.
Statistical Test of Hypothesis	p-Value	0.4414
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS mean
	Estimated Value	-0.125
	Confidence Interval	(2-Sided) 95%; -0.443 to 0.194
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Visual Acuity at Week 12 or Early Termination
Description	Visual acuity best-corrected (with glasses or best possible glasses prescription) was measured using early treatment diabetic retinopathy study (ETDRS) charts. There were 2 ETDRS charts. The letters on chart A were read using the right eye and on chart B using the left eye. The participants started from the top of the chart to down. The participants read down the chart until they reached a row where a minimum of 3 letters on a line could not be read. The participants were scored by number of letters identified correctly. Range was from 0 to 70, with higher scores indicate better visual acuity. As planned, for each participant, the worst eye (eye with the greatest decrease in visual acuity) was used in the analysis and data is reported for same.
Time Frame	Baseline, Week 12 or Early Termination (any time up to Week 12)

Outcome Measure Data

Analysis Population Description

ITT population included all participants randomized to treatment, who received at least 1 dose of study medication. Here, "Overall Number of Participants Analyzed" refers to those participants who were evaluable for this outcome measure.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants were randomized to receive pregabalin. In Week 1 (titration), participants received pregabalin 150 mg/day as 75 mg oral capsules twice daily. From Week 2 to 12, participants received pregabalin 300 mg/day as 150 mg oral capsules twice daily. In Week 13 (tapering), participants received 150 mg/day as 75 mg oral capsules twice daily. Participants were followed up from Week 14 to 15. If participants not tolerated 300 mg/day dose, they were discontinued from the study.	Participants were randomized to receive placebo matched to pregabalin from Week 1 to 13 and were followed up from Week 14 to 15.
Measure Participants	83	94
Least Squares Mean (Standard Error) [Letters identified correctly]	-1.890 (0.5515)	-0.990 (0.5057)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	ANCOVA with treatment and center in the model and the baseline visual acuity as the covariate was used to construct a 2-sided 95% confidence interval on the difference in LS mean between pregabalin and placebo.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1346
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS mean
	Estimated Value	-0.900
	Confidence Interval	(2-Sided) 95%; -2.083 to 0.283
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Baseline up to Week 15
Adverse Event Reporting Description	Same event may appear as both an adverse event and serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis performed on all participants randomized to treatment, who received at least 1 dose of study medication.
Arm/Group Title	Pregabalin		Placebo
Arm/Group Description	Participants were randomized to receive pregabalin. In Week 1 (titration), participants received pregabalin 150 mg/day as 75 mg oral capsules twice daily. From Week 2 to 12, participants received pregabalin 300 mg/day as 150 mg oral capsules twice daily. In Week 13 (tapering), participants received 150 mg/day as 75 mg oral capsules twice daily. Participants were followed up from Week 14 to 15. If participants not tolerated 300 mg/day dose, they were discontinued from the study.		Participants were randomized to receive placebo matched to pregabalin from Week 1 to 13 and were followed up from Week 14 to 15.
All Cause Mortality
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/89 (1.1%)		0/98 (0%)
Serious Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/89 (4.5%)		1/98 (1%)
Infections and infestations
Pneumonia	1/89 (1.1%)		0/98 (0%)
Nervous system disorders
Generalised tonic-clonic seizure	1/89 (1.1%)		0/98 (0%)
Postictal state	1/89 (1.1%)		0/98 (0%)
Status epilepticus	1/89 (1.1%)		0/98 (0%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/89 (0%)		1/98 (1%)
Psychiatric disorders
Major depression	1/89 (1.1%)		0/98 (0%)
Suicidal ideation	1/89 (1.1%)		0/98 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/89 (1.1%)		0/98 (0%)
Other (Not Including Serious) Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/89 (37.1%)		13/98 (13.3%)
General disorders
Fatigue	6/89 (6.7%)		3/98 (3.1%)
Investigations
Weight increased	5/89 (5.6%)		2/98 (2%)
Nervous system disorders
Dizziness	20/89 (22.5%)		3/98 (3.1%)
Headache	3/89 (3.4%)		5/98 (5.1%)
Somnolence	7/89 (7.9%)		3/98 (3.1%)

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.