Pregabalin in the Treatment of Patients With Generalized... | NCT00413010

NCT00413010

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Arm 2	Placebo Comparator		Drug: placebo
Arm 1	Experimental		Drug: pregabalin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
pregabalin	Drug	pregabalin 150-600 mg/day flexibly dosed for the first 6 weeks and fixed dosed for the last 2 weeks of total 8 weeks of double blind study period, + concurrent GAD treatment from the open-label study period

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Hamilton Anxiety Rating Scale (HAM-A) Total Scores	Change from baseline: average across visit weeks using mixed model. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety.	Baseline, 8 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change in HAM-A Total Score at Weekly Visits	Change: score at each study week minus score at baseline. HAM-A, a clinician-rated interview, measures presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety.	Baseline, Weeks 1 through Week 8

Eligibility Module

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Arcadia	California	91007-3462	United States
Pfizer Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22302014	Derived	Rickels K, Shiovitz TM, Ramey TS, Weaver JJ, Knapp LE, Miceli JJ. Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. Int Clin Psychopharmacol. 2012 May;27(3):142-50. doi: 10.1097/YIC.0b013e328350b133.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
BG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-7.6± 0.35 OG001-6.4± 0.36

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	Null hypothesis: no difference between Pregabalin (150-600 mg/day) BID and Placebo BID treatment groups. An initial sample size of 173 subjects per double-blind treatment group was calculated to provide at least 90% power to detect an effect size (ie, difference in the true means between 2 treatment groups/standard deviation) of 0.36 for the HAM-A total score change from Baseline using a 2-sided nominal significance level of 4.9%.	Mixed Models Analysis	Adjusted for treatment, pooled center baseline, HAM-A total score,time,and treatment-by time			Mean Difference (Final Values)	-1.2	Standard Error of the Mean	0.48		95	-2.16	-0.26			Since an interim analysis was conducted and the sample size was larger than the targeted 173 subjects per group, a critical t-value adjustment was 1.977, yielding an adjusted 95% CI shown above.

Secondary

Change in HAM-A Total Score at Weekly Visits

Change: score at each study week minus score at baseline. HAM-A, a clinician-rated interview, measures presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges from 0 to 56; higher score indicates greater anxiety.

Posted

Least Squares Mean

Standard Error

score on scale

Baseline, Weeks 1 through Week 8

ID	Title	Description
OG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
OG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Secondary

Number of Responders Using Hamilton Anxiety Rating Scale (HAM-A)

Responders = YES if subjects achieved a >= 50% decrease in HAM-A total score from Baseline to respective study week. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; higher score indicates greater anxiety.

Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.

Posted

Number

participants

Weeks 1 through Week 8

ID	Title	Description
OG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
OG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Secondary

Subjects in Remission Using Hamilton Anxiety Rating Scale (HAM-A) Total Score

Participant in remission defined as HAM-A total score of <= 7. HAM-A=clinician-rated interview measuring presence of anxiety-related symptoms in 14 areas including anxiety, tension, depressed mood, palpitations, breathing difficulties, sleep disturbances, & restlessness. Total score ranges 0 - 56; higher score indicates greater anxiety.

Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.

Posted

Number

participants

Week 1 through Week 8

ID	Title	Description
OG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
OG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Secondary

Time to Onset of Sustained Hamilton Anxiety Rating Scale (HAM-A) Improvement

Time to sustained improvement was defined as time to 50% or greater reduction in HAM-A total score from Baseline, which was sustained for the remainder of the study. HAM-A is a clinician-rated interview measuring the presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56; a higher score indicates greater anxiety.

Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment. CI for placebo patients was not estimable.

Posted

Median

95% Confidence Interval

days

Week 8

ID	Title	Description
OG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
OG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Secondary

Number of Responders Using Clinical Global Impression of Improvement (CGI-I) Score

Responders = YES using CGI-I if score indicated much improved or very much improved at the last study week. CGI-I is a clinician-rated instrument that measures change in subject's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.

Posted

Number

participants

Week 1 through Week 8

ID	Title	Description
OG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
OG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Secondary

Clinical Global Impression of Severity (CGI-S) Score

CGI-S is a clinician-rated instrument measuring the severity of a subject's symptoms on a 7-point categorical scale. Scores range from 1 (not at all ill) to 7 (among the most extremely ill patients). Higher score indicates that the subject is more ill.

Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.

Posted

Number

participants

Week 8

ID	Title	Description
OG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
OG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Secondary

Change in Hamilton Depression Rating Scale (HAM-D) Total Score

Change: score at each study week minus score at baseline. HAM-D, clinician-rated interview, measures presence of depressive symptoms in 17 areas (symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels, & weight loss). Total score ranges from 0 to 52; higher scores indicate more depression.

Intent-to-Treat (ITT) population included all randomized subjects who had received at least 1 dose of the double-blind treatment, and had a baseline and post-baseline efficacy assessment.

Posted

Least Squares Mean

Standard Error

score on scale

Weeks 1 through Week 8

ID	Title	Description
OG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).
OG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pregabalin	Pregabalin doses of 150 milligrams (mg)/day, 300 mg/day, 450 mg/day, and 600 mg/day was administered orally, twice daily (BID), with or without food, during the double-blind phase. Flexible dosing of pregabalin was allowed during the first 6 weeks; fixed dosing was required for the last 2 weeks of this period.Subjects were required to remain on a stable dose of their concurrent Generalized Anxiety Disorder (GAD) treatment (ie, escitalopram, paroxetine, or venlafaxine XR).			1		81
EG001	Placebo	Placebo was administrated orally, twice daily (BID) with or without food, during the double-blind phase. Subjects were required to remain on a stable dose of their concurrent GAD treatment (ie, escitalopram, paroxetine, or venlafaxine XR).			3		59

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Cardiac failure congestive	Cardiac disorders	Systematic Assessment	EG0001 affected180 at risk EG0010 affected176 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0001 affected180 at risk EG0010 affected176 at risk
Chronic Obstructive Pulmonary Disease (COPD)	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected180 at risk EG0010 affected176 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0000 affected180 at risk EG0011 affected176 at risk
Abdominal pain upper	Gastrointestinal disorders	Systematic Assessment	EG0000 affected180 at risk EG0011 affected176 at risk
Lower limb fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected180 at risk EG0011 affected176 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected180 at risk EG0011 affected176 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Vision blurred	Eye disorders	Systematic Assessment	EG0008 affected180 at risk EG0012 affected176 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0005 affected180 at risk EG0013 affected176 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0007 affected180 at risk EG0017 affected176 at risk
Dry mouth	Gastrointestinal disorders	Systematic Assessment	EG0004 affected180 at risk EG0012 affected176 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0006 affected180 at risk EG0011 affected176 at risk
Flatulence	Gastrointestinal disorders	Systematic Assessment	EG0004 affected180 at risk EG0010 affected176 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00013 affected180 at risk EG0018 affected176 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0002 affected180 at risk EG0014 affected176 at risk
Fatigue	General disorders	Systematic Assessment	EG0007 affected180 at risk EG0015 affected176 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0005 affected180 at risk EG0016 affected176 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0003 affected180 at risk EG0016 affected176 at risk
Weight increased	Investigations	Systematic Assessment	EG0004 affected180 at risk EG0010 affected176 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0005 affected180 at risk EG0011 affected176 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG00021 affected180 at risk EG00110 affected176 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00017 affected180 at risk EG0017 affected176 at risk
Paraesthesia	Nervous system disorders	Systematic Assessment	EG0004 affected180 at risk EG0011 affected176 at risk
Sedation	Nervous system disorders	Systematic Assessment	EG0007 affected180 at risk EG0017 affected176 at risk
Somnolence	Nervous system disorders	Systematic Assessment	EG00015 affected180 at risk EG0016 affected176 at risk
Euphoric mood	Psychiatric disorders	Systematic Assessment	EG0004 affected180 at risk EG0010 affected176 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0005 affected180 at risk EG0011 affected176 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected180 at risk EG0016 affected176 at risk

Further enrollment in this study was stopped based on the recommendation of an independent Data Monitoring Committee (DMC). An interim data analysis did not suggest the potential for robust efficacy. The study was not stopped for any safety findings.

Certain Agreements

ID	Term
D000098647	Generalized Anxiety Disorder

ID	Term
D000069583	Pregabalin

Ancestor Terms

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

Units	Counts
Participants	OG000177 OG001176

Units	Counts
Participants	OG000177 OG001176

Units	Counts
Participants	OG000177 OG001176

ID	Term
D001008	Anxiety Disorders
D001523	Mental Disorders