Efficacy and Safety of Pregabalin vs Placebo for Generali... | NCT00368745

Label	Type	Description	Intervention Names
Pregabalin	Active Comparator	Pregabalin treatment for GAD during 6 week taper/discontinuation from alprazolam treatment; followed by 6 weeks pregabalin treatment 'alprazolam free'.	Drug: Pregabalin
Placebo	Placebo Comparator	Placebo treatment of GAD during 6 week taper/discontinuation of alprazolam treatment followed by 6 weeks continuation of placebo treatment 'alprazolam free'.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Pregabalin	Drug	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.

Measure	Description	Time Frame
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	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).	Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)

Measure	Description	Time Frame
Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores	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.	Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		San Pedro	Provincia de San José	00	Costa Rica
Pfizer Investigational Site

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Pregabalin 75 mg to 300 mg PO BID	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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).

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.

Posted

Number

participants

Endpoint (Post Alprazolam Free Week 6 or LOCF Post Alprazolam Free Week 1)

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Units	Counts
Participants	OG00037 OG00127

Title

Denominators

Categories

Title	Measurements
	OG00020 OG00110

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Primary objective: evaluate the efficacy of pregabalin in maintaining the benzodiazepine free state in subjects with prior stable alprazolam use.	Cochran-Mantel-Haenszel	Cochran-Mantel-Haenszel (CMH) with country as a covariate	0.2838	significance determined using 2-tailed significance level of 0.05						95							Superiority or Other (legacy)

Secondary

Mean Change From Baseline in Hamilton Anxiety Scale (HAM-A) Scores

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.

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.

Posted

Least Squares Mean

Standard Error

scores on scale

Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (Alprazolam Free [AF] Week 6)

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Number of Subjects With > = 6 Point Increase in Physician's Withdrawal Checklist (PWC) Scores

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.

ITT; data not analyzed: PWC not measured at baseline.

Posted

Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Number of Subjects With > = 5 New PWC Symptoms

ITT; data not analyzed: PWC not measured at baseline.

Posted

Baseline, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Post-Hoc

Mean Scores Physician's Withdrawal Checklist (PWC)

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.

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.

Posted

Least Squares Mean

Standard Error

scores on scale

Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6 )

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001

Secondary

Mean Change From Baseline in Physician's Withdrawal Checklist (PWC) Scores

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.

Posted

Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, Endpoint (AF Week 6)

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Mean Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Scores.

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.

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.

Posted

Least Squares Mean

Standard Error

scores on scale

Baseline, Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Mean Scores for Clinical Global Impression-Improvement (CGI-I) Scale

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.

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.

Posted

Least Squares Mean

Standard Error

scores on scale

Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Mean Scores for Patient Global Impression-Improvement (PGI-I)

PGI-I: subject rated 7-point scale measures change in overall status; range 1 (very much improved) to 7 (very much worse).

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

Posted

Least Squares Mean

Standard Error

scores on scale

Alprazolam Taper Weeks 1 through 6, Alprazolam Free Weeks 1 through 6, and Endpoint (AF Week 6 )

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Mean Change From Baseline in Digit Symbol Substitution Test (DSST) Scores

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.

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

Posted

Least Squares Mean

Standard Error

scores on scale

Baseline, Endpoint (AF Week 6 )

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID

Secondary

Time to Discontinuation

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.

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

Posted

Number

days

Baseline, Week 13 (Final Visit/Early Termination)

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Time to First Use of Rescue Medication

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.

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

Posted

Number

days

Baseline, Week 13 (Final Visit/Early Termination)

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

Secondary

Number of Subjects in Relapse Free State at 6-week Benzodiazepine-free Endpoint (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.

ITT; endpoint = AF Week 6 or LOCF.

Posted

Number

participants

Alprazolam Free Week 6

ID	Title	Description
OG000	Pregabalin 75 mg to 300 mg PO BID	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.
OG001	Placebo 75 mg to 300 mg PO BID	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.

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pregabalin 75 mg to 300 mg PO BID	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.			0	56	33	56
EG001	Placebo 75 mg to 300 mg PO BID	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.			0	50	29	50

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hyperacusis	Ear and labyrinth disorders	MedDRA v11.1	Systematic Assessment	EG0003 affected56 at risk EG0011 affected50 at risk
Vision blurred	Eye disorders		Systematic Assessment	EG0005 affected56 at risk EG0012 affected50 at risk
Diarrhoea	Gastrointestinal disorders		Systematic Assessment	EG0003 affected56 at risk EG0015 affected50 at risk
Nausea	Gastrointestinal disorders		Systematic Assessment	EG0005 affected56 at risk EG0017 affected50 at risk
Vomiting	Gastrointestinal disorders		Systematic Assessment	EG0003 affected56 at risk EG0010 affected50 at risk
Asthenia	General disorders		Systematic Assessment	EG0003 affected56 at risk EG0015 affected50 at risk
Fatigue	General disorders		Systematic Assessment	EG0002 affected56 at risk EG0013 affected50 at risk
Irritability	General disorders		Systematic Assessment	EG0000 affected56 at risk EG0014 affected50 at risk
Oedema peripheral	General disorders		Systematic Assessment	EG0005 affected56 at risk EG0010 affected50 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders		Systematic Assessment	EG0003 affected56 at risk EG0010 affected50 at risk
Dizziness	Nervous system disorders		Systematic Assessment	EG00012 affected56 at risk EG0013 affected50 at risk
Headache	Nervous system disorders		Systematic Assessment	EG0007 affected56 at risk EG00113 affected50 at risk
Paraesthesia	Nervous system disorders		Non-systematic Assessment	EG0006 affected56 at risk EG0010 affected50 at risk
Somnolence	Nervous system disorders		Systematic Assessment	EG0003 affected56 at risk EG0012 affected50 at risk
Tremor	Nervous system disorders		Systematic Assessment	EG0002 affected56 at risk EG0014 affected50 at risk
Anxiety	Psychiatric disorders		Systematic Assessment	EG00011 affected56 at risk EG00110 affected50 at risk
Insomnia	Psychiatric disorders		Systematic Assessment	EG0004 affected56 at risk EG0017 affected50 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders		Systematic Assessment	EG0003 affected56 at risk EG0010 affected50 at risk

ID	Term
D001008	Anxiety Disorders
D001523	Mental Disorders

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	Pregabalin 75 mg to 300 mg PO BID	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.
BG001	Placebo 75 mg to 300 mg PO BID	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.
BG002	Total	Total of all reporting groups