Efficacy and Safety of Pregabalin vs Placebo for Generalized Anxiety Disorder (GAD) Symptoms in Subjects Discontinuing Benzodiazepine Treatment and Remaining 6 Weeks on Study Medication, Free From Benzodiazepine Use.

Sponsor

Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00368745

Collaborator

(none)

108

Enrollment

Locations

Arms

Duration (Months)

5.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

GAD subjects maintained on a stable dose of alprazolam for at least four weeks who meet eligibility criteria will be randomized to receive pregabalin vs matching placebo while simultaneously tapering off of alprazolam over 6 weeks. Subjects return weekly for assessment of safety/tolerability of pregabalin vs placebo as well as for assessment of anxiety and benzodiazepine withdrawal symptoms. Subjects successfully able to discontinue alprazolam, will continue 6 weeks of treatment with pregabalin vs placebo (free of benzodiazepine use). The efficacy and safety of pregabalin vs placebo for anxiety symptoms and ability to discontinue/remain free of alprazolam will be compared among pregabalin and placebo treated groups. Hypothesis is that a greater proportion of subjects will be successful in discontinuing and remaining free from benzodiazepines who were treated with pregabalin as compared to subjects treated with placebo.

Condition or Disease	Intervention/Treatment	Phase
Generalized Anxiety Disorder	Drug: Pregabalin Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Pregabalin in Subjects With Generalized Anxiety Disorder (GAD) Switching From Benzodiazepine Therapy.

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Aug 1, 2008

Actual Study Completion Date :

Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pregabalin Pregabalin treatment for GAD during 6 week taper/discontinuation from alprazolam treatment; followed by 6 weeks pregabalin treatment 'alprazolam free'.	Drug: Pregabalin GAD subjects on stable dose of alprazolam will be randomized to double-blind pregabalin at starting dose of 75mg twice daily. Weekly assessments of tolerability, need for rescue medication, anxiety/withdrawal symptoms will guide flexible dose titration of pregabalin at dose range between 75 and 300mg twice daily. Subjects successful in discontinuation of alprazolam while treated with pregabalin will continue to be maintained on pregabalin for 6 weeks and assessed weekly for ability to remain in the study. Other Names: Lyrica
Placebo Comparator: Placebo Placebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'.	Drug: Placebo GAD subjects on stable dose of alprazolam will be randomized to double-blind placebo matching assessments and study medication titration as detailed under the pregabalin arm description. Subjects successful in discontinuation of alprazolam while treated with placebo will continue to be maintained on placebo for 6 weeks and assessed weekly for ability to remain in the study.

Arm

Intervention/Treatment

Active Comparator: Pregabalin

Pregabalin treatment for GAD during 6 week taper/discontinuation from alprazolam treatment; followed by 6 weeks pregabalin treatment 'alprazolam free'.

Drug: Pregabalin

GAD subjects on stable dose of alprazolam will be randomized to double-blind pregabalin at starting dose of 75mg twice daily. Weekly assessments of tolerability, need for rescue medication, anxiety/withdrawal symptoms will guide flexible dose titration of pregabalin at dose range between 75 and 300mg twice daily. Subjects successful in discontinuation of alprazolam while treated with pregabalin will continue to be maintained on pregabalin for 6 weeks and assessed weekly for ability to remain in the study.

Other Names:

Lyrica

Placebo Comparator: Placebo

Placebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'.

Drug: Placebo

GAD subjects on stable dose of alprazolam will be randomized to double-blind placebo matching assessments and study medication titration as detailed under the pregabalin arm description. Subjects successful in discontinuation of alprazolam while treated with placebo will continue to be maintained on placebo for 6 weeks and assessed weekly for ability to remain in the study.

Outcome Measures

Primary Outcome Measures

Number of Subjects at Endpoint (Post Alprazolam Free Week 6 or Last Observation Carried Forward [LOCF] Post Alprazolam Free Week 1) Who Are Benzodiazepine Free [Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)]
Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine benzodiazepine psychoactive toxicology assay (each visit Alprazolam Free phase); negative serum benzodiazepine alcohol assay (endpoint or LOCF).

Secondary Outcome Measures

Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores [Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)]
HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); lower score indicates less affected. Change from baseline: mean at observation minus mean at baseline.
Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores [Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)]
PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Number of Subjects With > = 5 New PWC Symptoms [Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)]
PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores [Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)]
PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Change from baseline not analyzed as PWC was not measured at baseline. Mean PWS scores presented in Post-hoc outcome measure Mean PWS scores.
Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores. [Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )]
CGI-S: 7-point scale to assess global change in subject condition compared to baseline; range 1 (no evidence of illness) to 7 (among the most severely ill); higher score = more affected. Change from baseline: mean at observation minus mean at baseline.
Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale [Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )]
CGI-I: 7-point scale to assess global change in subject condition compared to baseline; range 1 (very much improved) to 7 (very much worse); higher score = more affected.
Mean Scores for Patient Global Impression-Improvement (PGI-I) [Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )]
PGI-I: subject rated 7-point scale measures change in overall status; range 1 (very much improved) to 7 (very much worse).
Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores [Baseline, Endpoint (AF Week 6 )]
DSST: subject-rated; evaluates aspects of cognition (includes attending to directions, processing speed, sustained attention, visual-motor integration, learning and psychomotor speed). Subject matches symbol (1 to 9) with corresponding number key (1 to 9); number of correct symbol-number pairs completed by subject over a 90-second test period determines DSST score. Change: mean at observation minus mean at baseline. Data summarized as change from baseline to endpoint.
Time to Discontinuation [Baseline, Week 13 (Final Visit/Early Termination)]
The 25th percentile estimate of time until discontinuation is based on Kaplan-Meier estimates. Event day is the study day when the subject discontinued from study.
Time to First Use of Rescue Medication [Baseline, Week 13 (Final Visit/Early Termination)]
The 25th percentile estimate of time until first use of rescue medication is based on Kaplan-Meier estimates. Event day is the study day when the subject first used rescue medication. Rescue medication: packet with 2 doses alprazolam to take only in the event subject experiences severe symptoms of benzodiazepine withdrawal or rebound anxiety.
Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (Alprazolam Free Week 6) [Alprazolam Free Week 6]
Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine toxicology assay (each visit Alprazolam Free phase), negative urine alcohol assay (Alprazolam Free Week 6 = endpoint or LOCF). Relapse: > = 2 intakes rescue medication, positive urine and /or alcohol assays, unable to tolerate alprazolam taper, or discontinuation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provide written informed consent
18-65 years old
male and female
A primary lifetime diagnosis of DSM-IV-TR (2000) GAD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition)

Exclusion Criteria:

Pregnant or lactating women
History of non-response to alprazolam, other benzodiazepines, gabapentin or pregabalin given for the treatment of anxiety as indicated by a (screening or baseline) Hamilton Anxiety Scale (HAM-A) score > 18

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	San Pedro De Montes De Oca	San José	Costa Rica	00
2	Pfizer Investigational Site	Plzen		Czechia	301 00
3	Pfizer Investigational Site	Praha 10		Czechia	100 00
4	Pfizer Investigational Site	Praha 6		Czechia	163 00
5	Pfizer Investigational Site	Praha 7		Czechia	170 00
6	Pfizer Investigational Site	Praha-Bubenec		Czechia	170 00
7	Pfizer Investigational Site	Paris	Cedex 12	France	75571
8	Pfizer Investigational Site	Arcachon		France	33120
9	Pfizer Investigational Site	Caen		France	14000
10	Pfizer Investigational Site	Elancourt		France	78990
11	Pfizer Investigational Site	Nantes-Orvault		France	44700
12	Pfizer Investigational Site	Guatemala		Guatemala
13	Pfizer Investigational Site	L'Aquila		Italy	67100
14	Pfizer Investigational Site	Milan		Italy	20157
15	Pfizer Investigational Site	Tepic	Nayarit	Mexico	63000
16	Pfizer Investigational Site	Mexico D.F.		Mexico	03740
17	Pfizer Investigational Site	San Luis Potosi		Mexico	78216
18	Pfizer Investigational Site	Langreo	Asturias	Spain	33900
19	Pfizer Investigational Site	Barcelona		Spain	08025
20	Pfizer Investigational Site	Barcelona		Spain	08036
21	Pfizer Investigational Site	Zamora		Spain	49021

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)

None provided.

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:

NCT00368745

Other Study ID Numbers:

A0081092

First Posted:

Aug 25, 2006

Last Update Posted:

Feb 9, 2021

Last Verified:

Nov 1, 2009

Additional relevant MeSH terms:

Anxiety Disorders

Pregabalin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Prior to randomization, subjects were stabilized on a therapeutic dose of open-label alprazolam (minimum of 2 weeks) if they entered the study on a stable alprazolam dose or for up to 4 weeks if entered on a different benzodiazepine. Alprazolam dose range during 2-4 week stabilization phase was 1-4 milligrams (mg) by mouth (PO) twice a day (BID).

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Period Title: Randomized to Double-blind Treatment
STARTED	57	51
COMPLETED	56	50
NOT COMPLETED	1	1
Period Title: Randomized to Double-blind Treatment
STARTED	56	50
COMPLETED	30	19
NOT COMPLETED	26	31

Baseline Characteristics

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID	Total
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.	Total of all reporting groups
Overall Participants	56	50	106
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.1 (10.6)	43.5 (11.3)	41.7 (11.0)
Sex: Female, Male (Count of Participants)
Female	42 75%	34 68%	76 71.7%
Male	14 25%	16 32%	30 28.3%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects at Endpoint (Post Alprazolam Free Week 6 or Last Observation Carried Forward [LOCF] Post Alprazolam Free Week 1) Who Are Benzodiazepine Free
Description	Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine benzodiazepine psychoactive toxicology assay (each visit Alprazolam Free phase); negative serum benzodiazepine alcohol assay (endpoint or LOCF).
Time Frame	Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)

Outcome Measure Data

Analysis Population Description
Intent to Treat (ITT) population: received at least 1 dose pregabalin or placebo. Primary outcome ITT = all treated subjects in alprazolam free phase. Endpoint = Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	37	27
Number [participants]	20 35.7%	10 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Primary objective: evaluate the efficacy of pregabalin in maintaining the benzodiazepine free state in subjects with prior stable alprazolam use.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.2838
	Comments	significance determined using 2-tailed significance level of 0.05
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel (CMH) with country as a covariate

2. Secondary Outcome

Title	Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores
Description	HAM-A measures treatment-related changes in generalized anxiety symptoms; 14 item questionnaire scored 0 (not present) to 4 (very severe); lower score indicates less affected. Change from baseline: mean at observation minus mean at baseline.
Time Frame	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)

Outcome Measure Data

Analysis Population Description
ITT; subject has a baseline and at least 1 post-baseline measurement before week 13; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	46	41
Alprazolam Taper (AT) Week 1 (n=46, 40)	-0.82 (0.66)	0.67 (0.81)
AT Week 2 (n=45, 37)	-1.72 (0.98)	2.17 (1.15)
AT Week 3 (n=33, 26)	-2.59 (0.99)	-0.21 (1.32)
AT Week 4 (n=18, 11)	-1.47 (1.11)	1.91 (1.82)
AT Week 5 (n=8, 5)	-2.36 (2.19)	2.86 (2.97)
AT Week 6 (n=17, 9)	-1.26 (1.40)	2.41 (2.11)
Alprazolam Free (AF) Week 1 (n=39, 28)	-0.43 (0.90)	2.40 (1.15)
AF Week 2 (n=35, 24)	-2.15 (0.91)	-1.14 (1.19)
AF Week 3 (n=31, 26)	-3.46 (0.92)	-2.47 (1.14)
AF Week 4 (n=31, 19)	-3.58 (0.84)	-3.58 (1.14)
AF Week 5 (n=27, 18)	-3.85 (0.87)	-3.34 (1.18)
AF Week 6 (n=22, 15)	-5.62 (0.84)	-4.77 (1.05)
Endpoint [LOCF] (n=46, 41)	-2.01 (1.13)	2.77 (1.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Taper (AT) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0709
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	Least squares (LS) Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.48
	Confidence Interval	() 95% -3.10 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.81
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0006
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.89
	Confidence Interval	() 95% -6.04 to -1.74
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0718
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.38
	Confidence Interval	() 95% -4.98 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.30
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0920
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.38
	Confidence Interval	() 95% -7.37 to 0.60
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.92
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1371
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.22
	Confidence Interval	() 95% -12.67 to 2.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.04
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0882
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.68
	Confidence Interval	() 95% -7.96 to 0.61
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.04
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Free (AF) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0135
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.83
	Confidence Interval	() 95% -5.05 to -0.61
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.11
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3924
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.01
	Confidence Interval	() 95% -3.38 to 1.35
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.18
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3868
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.00
	Confidence Interval	() 95% -3.29 to 1.30
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.14
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.9966
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.00
	Confidence Interval	() 95% -2.31 to 2.32
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.15
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.6873
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.51
	Confidence Interval	() 95% -3.07 to 2.05
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.26
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.5337
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.85
	Confidence Interval	() 95% -3.62 to 1.91
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.35
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Endpoint [LOCF]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0008
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.79
	Confidence Interval	() 95% -7.51 to -2.07
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.37
	Estimation Comments

3. Secondary Outcome

Title	Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores
Description	PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Time Frame	Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)

Outcome Measure Data

Analysis Population Description
ITT; data not analyzed: PWC not measured at baseline.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Subjects With > = 5 New PWC Symptoms
Description	PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Data not analyzed: PWC not measured at baseline.
Time Frame	Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)

Outcome Measure Data

Analysis Population Description
ITT; data not analyzed: PWC not measured at baseline.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	0	0

5. Post-Hoc Outcome

Title	Mean Scores Physician's Withdrawal Checklist (PWC)
Description	Mean scores at each visit for PWC: 20-item physician-rated interview measures presence of anxiolytic drug withdrawal-related signs and symptoms (gastrointestinal, mood, sleep, motor, somatic, perception, and cognition); range 0 (not present) to 3 (severe). Total score: 0 to 60; higher score = more affected. Mean scores entered as post-hoc analysis as Mean change from baseline in PWS scores not analyzed: PWS not measured at baseline.
Time Frame	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6 )

Outcome Measure Data

Analysis Population Description
ITT; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively. Endpoint = AF Week 6 or LOCF. Refer to measure Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	46	41
Alprazolam Taper (AT) Week 1 (n=43, 40)	6.32 (1.40)	8.50 (1.45)
AT Week 2 (n=44,37)	6.37 (1.18)	10.00 (1.34)
AT Week 3 (n=33, 26)	6.56 (1.40)	9.41 (1.76)
AT Week 4 (n=18, 11)	5.63 (0.89)	9.04 (1.37)
AT Week 5 (n=7, 5)	7.30 (1.52)	9.58 (2.32)
AT Week 6 (n=17, 9)	6.82 (1.39)	12.55 (2.07)
Alprazolam Free (AF) Week 1 (n=39, 28)	6.78 (1.15)	10.70 (1.45)
AF Week 2 (n=33, 24)	4.71 (0.93)	6.43 (1.19)
AF Week 3 (n=30, 26)	6.86 (0.85)	7.16 (1.05)
AF Week 4 (n=30, 19)	7.43 (0.89)	6.99 (1.17)
AF Week 5 (n=27, 18)	7.87 (0.76)	8.25 (1.00)
AF Week 6 (n=22, 15)	2.40 (0.94)	5.51 (1.16)
Endpoint [LOCF] (n=46, 41)	6.48 (1.23)	10.28 (1.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Taper (AT) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1220
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.18
	Confidence Interval	() 95% -4.97 to 0.60
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.40
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0053
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.63
	Confidence Interval	() 95% -6.15 to -1.11
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.26
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1048
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.85
	Confidence Interval	() 95% -6.32 to 0.62
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.73
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0357
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.41
	Confidence Interval	() 95% -6.57 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.52
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.4263
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.28
	Confidence Interval	() 95% -8.82 to 4.26
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.67
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0104
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.73
	Confidence Interval	() 95% -9.96 to -1.51
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.02
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Free (AF) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0069
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.92
	Confidence Interval	() 95% -6.73 to -1.12
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.40
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.2185
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.71
	Confidence Interval	() 95% -4.47 to 1.05
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.37
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.7832
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.29
	Confidence Interval	() 95% -2.41 to 1.83
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.06
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.7062
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.44
	Confidence Interval	() 95% -1.90 to 2.79
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.16
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.7161
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	() 95% -2.49 to 1.73
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.04
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0376
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.11
	Confidence Interval	() 95% -6.03 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.43
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Endpoint [LOCF]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0122
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.80
	Confidence Interval	() 95% -6.74 to -0.85
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.48
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores
Description	PWC: 20 item physician rated interview (0 = not present; 3 = severe; score range: 0 to 60) measuring: signs of anxiolytic drug withdrawal and gastrointestinal (GI), mood, sleep, motor, somatic, perception and cognition symptoms. Change from baseline not analyzed as PWC was not measured at baseline. Mean PWS scores presented in Post-hoc outcome measure Mean PWS scores.
Time Frame	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)

Outcome Measure Data

Analysis Population Description
ITT; Change from baseline not analyzed as PWC was not measured at baseline. Mean PWS scores presented in Post-hoc outcome measure Mean PWS scores.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	0	0

7. Secondary Outcome

Title	Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores.
Description	CGI-S: 7-point scale to assess global change in subject condition compared to baseline; range 1 (no evidence of illness) to 7 (among the most severely ill); higher score = more affected. Change from baseline: mean at observation minus mean at baseline.
Time Frame	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )

Outcome Measure Data

Analysis Population Description
ITT; subject has a baseline and at least 1 post-baseline endpoint measurement; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	45	41
Alprazolam Taper (AT) Week 1 (n=45, 40)	-0.23 (0.13)	0.22 (0.15)
AT Week 2 (n=44, 37)	-0.33 (0.17)	0.41 (0.19)
AT Week 3 (n=32, 27)	-0.60 (0.20)	-0.10 (0.26)
AT Week 4 (n=17, 11)	-0.41 (0.21)	-0.04 (0.32)
AT Week 5 (n=7, 5)	-0.77 (0.27)	-0.05 (0.40)
AT Week 6 (n=16, 9)	-0.63 (0.32)	0.08 (0.43)
Alprazolam Free (AF) Week 1 (n=38, 28)	-0.46 (0.17)	0.23 (0.21)
AF Week 2 (n=34, 24)	-0.98 (0.20)	-0.48 (0.26)
AF Week 3 (n=30, 26)	-0.88 (0.22)	-0.32 (0.27)
AF Week 4 (n=30, 19)	-0.87 (0.18)	-0.84 (0.25)
AF Week 5 (n=26, 18)	-0.82 (0.19)	-0.75 (0.26)
AF Week 6 (n=21, 15)	-1.33 (0.20)	-1.02 (0.25)
Endpoint [LOCF] (n=45, 41)	-0.45 (0.21)	0.31 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Taper (AT) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0052
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.45
	Confidence Interval	() 95% -0.76 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.16
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.74
	Confidence Interval	() 95% -1.11 to -0.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.18
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0528
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.50
	Confidence Interval	() 95% -1.00 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.25
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3085
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	() 95% -1.11 to 0.37
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.35
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1807
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.72
	Confidence Interval	() 95% -1.92 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.47
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1074
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.71
	Confidence Interval	() 95% -1.58 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.42
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Free (AF) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0013
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.69
	Confidence Interval	() 95% -1.10 to -0.28
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.20
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0503
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.50
	Confidence Interval	() 95% -0.99 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.25
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0364
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.56
	Confidence Interval	() 95% -1.09 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.26
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.9140
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	() 95% -0.51 to 0.46
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.24
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.7789
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	() 95% -0.62 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.27
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3189
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.32
	Confidence Interval	() 95% -0.95 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.31
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Endpoint [LOCF]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0031
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.76
	Confidence Interval	() 95% -1.26 to -0.27
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.25
	Estimation Comments

8. Secondary Outcome

Title	Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale
Description	CGI-I: 7-point scale to assess global change in subject condition compared to baseline; range 1 (very much improved) to 7 (very much worse); higher score = more affected.
Time Frame	Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )

Outcome Measure Data

Analysis Population Description
ITT; subject has a baseline and endpoint measurement; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	46	41
Alprazolam Taper (AT) Week 1 (n=46, 39)	3.52 (0.20)	3.90 (0.24)
AT Week 2 (n=45, 37)	3.17 (0.27)	3.98 (0.31)
AT Week 3 (n=33, 27)	2.88 (0.31)	3.47 (0.39)
AT Week 4 (n=18, 11)	3.09 (0.35)	3.01 (0.54)
AT Week 5 (n=8, 5)	2.63 (0.30)	3.44 (0.47)
AT Week 6 (n=17, 9)	3.00 (0.31)	3.86 (0.46)
Alprazolam Free (AF) Week 1 (n=39, 28)	2.93 (0.28)	3.90 (0.36)
AF Week 2 (n=35, 24)	2.39 (0.28)	3.27 (0.35)
AF Week 3 (n=30, 26)	2.15 (0.28)	2.93 (0.35)
AF Week 4 (n=31, 19)	2.20 (0.29)	2.46 (0.39)
AF Week 5 (n=27, 18)	2.29 (0.32)	2.77 (0.42)
AF Week 6 (n=22, 15)	1.52 (0.28)	2.18 (0.34)
Endpoint [LOCF] (n= 46, 41)	2.57 (0.30)	3.52 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Taper (AT) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1260
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	() 95% -0.86 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.24
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0074
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.81
	Confidence Interval	() 95% -1.40 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.29
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1250
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.59
	Confidence Interval	() 95% -1.35 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.38
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.8991
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	() 95% -1.17 to 1.32
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.60
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1747
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.81
	Confidence Interval	() 95% -2.07 to 0.46
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.53
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0744
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.85
	Confidence Interval	() 95% -1.79 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.45
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Free (AF) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0063
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.98
	Confidence Interval	() 95% -1.67 to -0.29
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.35
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0140
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.87
	Confidence Interval	() 95% -1.56 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.34
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0267
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.78
	Confidence Interval	() 95% -1.46 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.34
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.5104
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.26
	Confidence Interval	() 95% -1.03 to 0.52
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.38
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.2702
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.48
	Confidence Interval	() 95% -1.35 to 0.39
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.43
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1241
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.66
	Confidence Interval	() 95% -1.52 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.42
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Endpoint [LOCF]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0109
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.95
	Confidence Interval	() 95% -1.67 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.36
	Estimation Comments

9. Secondary Outcome

Title	Mean Scores for Patient Global Impression-Improvement (PGI-I)
Description	PGI-I: subject rated 7-point scale measures change in overall status; range 1 (very much improved) to 7 (very much worse).
Time Frame	Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )

Outcome Measure Data

Analysis Population Description
ITT; endpoint = AF Week 6 or LOCF; (n) = number of subjects with data for analysis for pregabalin and placebo, respectively.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	46	41
Alprazolam Taper (AT) Week 1 (n=46, 40)	3.16 (0.23)	3.82 (0.27)
AT Week 2 (n= 45, 37)	3.13 (0.32)	4.03 (0.36)
AT Week 3 (n=33, 26)	2.93 (0.28)	3.31 (0.35)
AT Week 4 (n=18, 11)	3.12 (0.34)	2.98 (0.52)
AT Week 5 (n=8, 5)	2.91 (0.37)	3.75 (0.58)
AT Week 6 (n=17, 9)	2.93 (0.42)	3.38 (0.63)
Alprazolam Free (AF) Week 1 (n=39, 28)	2.95 (0.26)	3.45 (0.33)
AF Week 2 (n=35, 24)	2.34 (0.27)	2.94 (0.34)
AF Week 3 (n=31, 26)	2.28 (0.28)	2.92 (0.35)
AF Week 4 (n=30, 19)	2.43 (0.29)	2.73 (0.38)
AF Week 5 (n=27, 18)	2.32 (0.31)	2.70 (0.41)
AF Week 6 (n=22, 14)	1.53 (0.27)	2.48 (0.35)
Endpoint [LOCF] (n=46, 41)	2.71 (0.32)	3.74 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Taper (AT) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0226
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.66
	Confidence Interval	() 95% -1.22 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.28
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0099
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.90
	Confidence Interval	() 95% -1.58 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.34
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.2827
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	() 95% -1.07 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.35
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.8232
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.13
	Confidence Interval	() 95% -1.07 to 1.34
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.58
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.2409
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.85
	Confidence Interval	() 95% -2.41 to 0.72
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.66
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AT Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.4760
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.45
	Confidence Interval	() 95% -1.73 to 0.84
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.61
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Alprazolam Free (AF) Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1252
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.50
	Confidence Interval	() 95% -1.14 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.32
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0717
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.60
	Confidence Interval	() 95% -1.26 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.33
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0707
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.64
	Confidence Interval	() 95% -1.33 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.35
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.4341
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.30
	Confidence Interval	() 95% -1.08 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.39
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.3700
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	() 95% -1.23 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.42
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	AF Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0328
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.96
	Confidence Interval	() 95% -1.83 to -0.08
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.43
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments	Endpoint [LOCF]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0096
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country as covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.03
	Confidence Interval	() 95% -1.80 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.39
	Estimation Comments

10. Secondary Outcome

Title	Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores
Description	DSST: subject-rated; evaluates aspects of cognition (includes attending to directions, processing speed, sustained attention, visual-motor integration, learning and psychomotor speed). Subject matches symbol (1 to 9) with corresponding number key (1 to 9); number of correct symbol-number pairs completed by subject over a 90-second test period determines DSST score. Change: mean at observation minus mean at baseline. Data summarized as change from baseline to endpoint.
Time Frame	Baseline, Endpoint (AF Week 6 )

Outcome Measure Data

Analysis Population Description
ITT; subject has baseline and endpoint (final visit) measurement; endpoint = AF Week 6 or LOCF.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	33	29
Least Squares Mean (Standard Error) [scores on scale]	13.10 (2.64)	13.47 (2.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.8897
	Comments	contrasts performed using Dunnett's Test
	Method	ANCOVA
	Comments	LS Means from the ANCOVA model with treatment as the main effect and country and baseline as the covariate

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	() 95% -5.74 to 4.99
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.68
	Estimation Comments

11. Secondary Outcome

Title	Time to Discontinuation
Description	The 25th percentile estimate of time until discontinuation is based on Kaplan-Meier estimates. Event day is the study day when the subject discontinued from study.
Time Frame	Baseline, Week 13 (Final Visit/Early Termination)

Outcome Measure Data

Analysis Population Description
ITT; Week 13 (Final Visit/Early Termination) or LOCF.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	19	24
Number [days]	51	33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0626
	Comments	p-value is from the log-rank statistic from the tests for equality over treatment as strata and country used as covariate
	Method	Log Rank
	Comments

12. Secondary Outcome

Title	Time to First Use of Rescue Medication
Description	The 25th percentile estimate of time until first use of rescue medication is based on Kaplan-Meier estimates. Event day is the study day when the subject first used rescue medication. Rescue medication: packet with 2 doses alprazolam to take only in the event subject experiences severe symptoms of benzodiazepine withdrawal or rebound anxiety.
Time Frame	Baseline, Week 13 (Final Visit/Early Termination)

Outcome Measure Data

Analysis Population Description
ITT; Week 13 (Final Visit/Early Termination) or LOCF

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	11	17
Number [days]	63	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.0148
	Comments	p-value is from the log-rank statistic from the tests for equality over treatment as strata and country used as covariate
	Method	Log Rank
	Comments

13. Secondary Outcome

Title	Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (Alprazolam Free Week 6)
Description	Number of subjects benzodiazepine free: < 2 doses rescue medication; negative urine toxicology assay (each visit Alprazolam Free phase), negative urine alcohol assay (Alprazolam Free Week 6 = endpoint or LOCF). Relapse: > = 2 intakes rescue medication, positive urine and /or alcohol assays, unable to tolerate alprazolam taper, or discontinuation.
Time Frame	Alprazolam Free Week 6

Outcome Measure Data

Analysis Population Description
ITT; endpoint = AF Week 6 or LOCF.

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID	Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.	Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
Measure Participants	22	15
Number [participants]	21 37.5%	12 24%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin 75 mg to 300 mg PO BID, Placebo 75 mg to 300 mg PO BID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.1159
	Comments	p-value is obtained using Cochran-Mantel-Haenszel option
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

	Pregabalin 75 mg to 300 mg PO BID		Placebo 75 mg to 300 mg PO BID
Time Frame
Adverse Event Reporting Description

Arm/Group Title	Pregabalin 75 mg to 300 mg PO BID		Placebo 75 mg to 300 mg PO BID
Arm/Group Description	Pregabalin treatment following randomization to double-blind treatment: Baseline to Week 1: Pregabalin 75 mg PO BID (150 mg/day); Week 2: Pregabalin 150 mg PO BID (300 mg/day); Week 3 to Week 6 Pregabalin PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with pregabalin at the same dose as during the double-blind taper.		Placebo treatment following randomization to double-blind treatment: Baseline to Week 1: placebo 75 mg PO BID (150 mg/day); Week 2: placebo 150 mg PO BID (300 mg/day); Week 3 to Week 6 placebo PO dosing ranged from 150 to 600 mg/day, given BID; during double-blind the alprazolam dose was tapered with a 25% reduction each week from baseline up to 6 weeks depending on the starting dose of alprazolam and toleration of dose reduction. Subjects successfully discontinued from alprazolam, continued for an additional 6 weeks of double-blind treatment with placebo at the same dose as during the double-blind taper.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin 75 mg to 300 mg PO BID		Placebo 75 mg to 300 mg PO BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/56 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Pregabalin 75 mg to 300 mg PO BID		Placebo 75 mg to 300 mg PO BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/56 (58.9%)		29/50 (58%)
Ear and labyrinth disorders
Hyperacusis	3/56 (5.4%)		1/50 (2%)
Eye disorders
Vision blurred	5/56 (8.9%)		2/50 (4%)
Gastrointestinal disorders
Diarrhoea	3/56 (5.4%)		5/50 (10%)
Nausea	5/56 (8.9%)		7/50 (14%)
Vomiting	3/56 (5.4%)		0/50 (0%)
General disorders
Asthenia	3/56 (5.4%)		5/50 (10%)
Fatigue	2/56 (3.6%)		3/50 (6%)
Irritability	0/56 (0%)		4/50 (8%)
Oedema peripheral	5/56 (8.9%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	3/56 (5.4%)		0/50 (0%)
Nervous system disorders
Dizziness	12/56 (21.4%)		3/50 (6%)
Headache	7/56 (12.5%)		13/50 (26%)
Paraesthesia	6/56 (10.7%)		0/50 (0%)
Somnolence	3/56 (5.4%)		2/50 (4%)
Tremor	2/56 (3.6%)		4/50 (8%)
Psychiatric disorders
Anxiety	11/56 (19.6%)		10/50 (20%)
Insomnia	4/56 (7.1%)		7/50 (14%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/56 (5.4%)		0/50 (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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 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
Email	ClinicalTrials.govCallCenter@pfizer.com

Responsible Party:

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

ClinicalTrials.gov Identifier:

NCT00368745

Other Study ID Numbers:

A0081092

First Posted:

Aug 25, 2006

Last Update Posted:

Feb 9, 2021

Last Verified:

Nov 1, 2009