A Phase 3b Multicenter Study of Pregabalin in Fibromyalgi... | NCT01432236

ID	Type	Description	Link
2011-002480-19	EudraCT Number

Label	Type	Description	Intervention Names
Pregabalin	Experimental	Group 1 as Pregabalin vs. Placebo (cross over study in which period one has this group)	Drug: Pregabalin
Placebo	Placebo Comparator	Group 2 as placebo vs. pregabalin (cross over study in which period two will have this group)	Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
Pregabalin	Drug	Pregabalin 300 or 450 mg/day dosed BID ( twice a day) for 14 weeks; 150 mg/day starting dose	Pregabalin

Measure	Description	Time Frame
Mean NRS Pain Score at End of Period.	The daily pain diary consists of an 11-point numeric scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The endpoint mean pain scores for Period 1 and Period 2 are defined as the mean of the last 7 non-missing daily diary pain ratings while taking study medication in the double-blind phase during Period 1 and Period 2, respectively.	End of each period, at Weeks 6 and 14

Measure	Description	Time Frame
Fibromyalgia Impact Questionnaire (FIQ) Score at Baseline.	This was a 20-item participant reported outcome instrument. It contained 10 subscales, which were combined to yield a total score. The first 11 questions were related specifically to physical functioning subscale, ranging from 0 to 10. The remaining 9 questions assessed pain, fatigue, stiffness, difficulty working, and symptoms of anxiety and depression ranging from 0 to 10. The higher values indicated greater impairment. All 20 were combined to form a total score ranging from 0 to 100, provides an estimation of fibromyalgia impact with higher scores indicating more impairment. The severity categorizations for the FIQ are: less than 40 (mild), 40-60 (moderate), and above 60 (severe).

Measure	Description	Time Frame
PGIC at the End of Period 2.	PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). Because of the crossover design and PGIC recall period (since starting study medication), the Period 1 PGIC data were felt to provide the clearest comparison across treatments, whereas Period 2 PGIC data were felt to have a more complex interpretation. Thus PGIC at End of Period 2 was separately analyzed from PGIC at End of Period 1.

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

Facility	Status	City	State	ZIP	Country	Contacts
Genova Clinical Research		Tucson	Arizona	85704	United States
SDS Clinical Trials

PubMed Identifier	Type	Citation	Retractions
27057659	Derived	Bateman L, Sarzi-Puttini P, Burbridge CL, Landen JW, Masters ET, Bhadra Brown P, Scavone JM, Emir B, Vissing RS, Clair AG, Pauer LR. Burden of illness in fibromyalgia patients with comorbid depression. Clin Exp Rheumatol. 2016 Mar-Apr;34(2 Suppl 96):S106-13. Epub 2016 Mar 10.
26034150	Derived	Arnold LM, Sarzi-Puttini P, Arsenault P, Khan T, Bhadra Brown P, Clair A, Scavone JM, Driscoll J, Landen J, Pauer L. Efficacy and Safety of Pregabalin in Patients with Fibromyalgia and Comorbid Depression Taking Concurrent Antidepressant Medication: A Randomized, Placebo-controlled Study. J Rheumatol. 2015 Jul;42(7):1237-44. doi: 10.3899/jrheum.141196. Epub 2015 Jun 1.

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

ID	Title	Description
FG000	Pregabalin/Placebo	Participants were randomized in a 1:1 ratio to double-blind treatment with pregabalin for 6 weeks (3 weeks dose optimization and 3 weeks fixed dose) in period 1 followed by placebo in period 2 with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

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

Mean NRS Pain Score at End of Period.

The daily pain diary consists of an 11-point numeric scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The endpoint mean pain scores for Period 1 and Period 2 are defined as the mean of the last 7 non-missing daily diary pain ratings while taking study medication in the double-blind phase during Period 1 and Period 2, respectively.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Units on a scale

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo	The below table included participants who received placebo in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). There was a 2-week single-blind taper/washout period between treatment periods.

Units	Counts
Participants	OG000179 OG001173

Title

Denominators

Categories

Title	Measurements
	OG0004.84± 0.15 OG0015.45± 0.16

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	Analysis was done using a linear mixed effects model including sequence, period, and treatment as fixed factors and participant within sequence and within-participant error as random factors.	Mixed Models Analysis	Satterthwaite's approximation was used to estimate denominator degrees of freedom.	0.0001	Primary analysis was two-sided and performed at the 0.05 significance level.	Mean Difference (Final Values)	-0.61			2-Sided	95	-0.91	-0.31					Superiority or Other (legacy)

Secondary

Fibromyalgia Impact Questionnaire (FIQ) Score at Baseline.

This was a 20-item participant reported outcome instrument. It contained 10 subscales, which were combined to yield a total score. The first 11 questions were related specifically to physical functioning subscale, ranging from 0 to 10. The remaining 9 questions assessed pain, fatigue, stiffness, difficulty working, and symptoms of anxiety and depression ranging from 0 to 10. The higher values indicated greater impairment. All 20 were combined to form a total score ranging from 0 to 100, provides an estimation of fibromyalgia impact with higher scores indicating more impairment. The severity categorizations for the FIQ are: less than 40 (mild), 40-60 (moderate), and above 60 (severe).

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Deviation

Units on a scale

Baseline

ID	Title	Description
OG000	Pregabalin/Placebo	Participants were randomized in a 1:1 ratio to double-blind treatment with pregabalin for 6 weeks (3 weeks dose optimization and 3 weeks fixed dose) in period 1 followed by placebo in period 2 with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo/Pregabalin

Secondary

FIQ Score at End of Period.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation. Different number (N) for each category represents participants that were actually treated with pregabalin and placebo during the study.

Posted

Least Squares Mean

Standard Error

Units on a scale

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Secondary

Patient Global Impression of Change (PGIC) at the End of Period 1.

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse).

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Number

Percentage of participants

End of Period 1 at Week 6

ID	Title	Description
OG000	Pregabalin	This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo	This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). There was a 2-week single-blind taper/washout period between treatment periods.

Other Pre-specified

PGIC at the End of Period 2.

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). Because of the crossover design and PGIC recall period (since starting study medication), the Period 1 PGIC data were felt to provide the clearest comparison across treatments, whereas Period 2 PGIC data were felt to have a more complex interpretation. Thus PGIC at End of Period 2 was separately analyzed from PGIC at End of Period 1.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Number

Percentage of Participants

End of Period 2 at Week 14

ID	Title	Description
OG000	Pregabalin	This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo	This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Secondary

Percentage of Participants With >=30% and >=50% Pain Reduction Based on Daily Pain Diary.

Participant with at least a 30% reduction in mean pain score from baseline (at randomization) to the endpoint at the end of each period (Visits 6 and 12) is considered a 30% responder, for the respective period. Similarly, a subject with at least a 50% reduction in mean pain score from baseline (at randomization) to the endpoint at the end of each period (Visits 6 and 12) is considered a 50% responder, for the respective period.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Number

Percentage of participants

Visits 2, 6, and 12

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo

Secondary

Subjective Sleep Questionnaire - Mean Sleep Quality at End of Period.

Subjective Sleep Questionnaire included 5 items: participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Subjective rating of quality of sleep during the past night was done by selecting a number between 0 (very poor) and 10 (excellent). Mean sleep quality was calculated as the mean of the last seven days, the potential range of responses was therefore 0-10.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Units on a scale

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Secondary

Subjective Sleep Questionnaire - Mean Subjective Wake After Sleep Onset at End of Period.

Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective wake after sleep onset was the subjective estimate of the total amount of time the participant was awake after initial sleep onset until final awakening.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Minutes

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001

Secondary

Subjective Sleep Questionnaire - Mean Latency to Sleep Onset at End of Period.

Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective latency to sleep onset was the subjective estimate of the amount of time to fall asleep after lights out.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Minutes

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo

Secondary

Subjective Sleep Questionnaire - Mean Subjective Total Sleep Time at End of Period.

Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective total sleep time was the subjective estimate of the total amount of time the participant was asleep after lights out until final awakening.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Minutes

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo

Secondary

Subjective Sleep Questionnaire - Parameter Estimates for Subjective Number of Awakenings Per Night After Sleep Onset at End of Period.

Subjective Sleep Questionnaire included, participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (numeric rating scale) for the previous night. Subjective number of awakenings after sleep onset was the subjective estimate of the total number of times the participant awakened during the night until final awakening.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Number of times awakened

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Secondary

Hospital Anxiety and Depression Scale (HADS) at Baseline.

HADS: participant rated questionnaire with 2 subscales. HADS-A (anxiety) assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D (depression) assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Deviation

Units on a scale

Baseline

ID	Title	Description
OG000	Pregabalin/Placebo	Participants were randomized in a 1:1 ratio to double-blind treatment with pregabalin for 6 weeks (3 weeks dose optimization and 3 weeks fixed dose) in period 1 followed by placebo in period 2 with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo/Pregabalin	Participants were randomized in a 1:1 ratio to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (3 weeks dose optimization and 3 weeks fixed dose) with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Secondary

HADS at End of Period.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Units on a scale

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001

Secondary

Mean EuroQoL 5-Dimensions (EQ-5D) Score at Baseline.

EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point visual analog scale (0=worst, 100=best). EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Deviation

Units on a scale

Baseline

ID	Title	Description
OG000	Pregabalin/Placebo	Participants were randomized in a 1:1 ratio to double-blind treatment with pregabalin for 6 weeks (3 weeks dose optimization and 3 weeks fixed dose) in period 1 followed by placebo in period 2 with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo/Pregabalin	Participants were randomized in a 1:1 ratio to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (3 weeks dose optimization and 3 weeks fixed dose) with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Secondary

EQ-5D Score at End of Period.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Units on a scale

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Other Pre-specified

Mean Patient Static Global Assessment (PSGA) Score at Baseline.

PSGA was a single-item self-rated instrument that measured the participant's overall status on an 11-point NRS ranging from 0 (very poor) to 10 (very good).

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Deviation

Units on a scale

Baseline

ID	Title	Description
OG000	Pregabalin/Placebo	Participants were randomized in a 1:1 ratio to double-blind treatment with pregabalin for 6 weeks (3 weeks dose optimization and 3 weeks fixed dose) in period 1 followed by placebo in period 2 with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo/Pregabalin	Participants were randomized in a 1:1 ratio to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (3 weeks dose optimization and 3 weeks fixed dose) with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Other Pre-specified

Mean PSGA Score at End of Period.

PSGA was a single-item self-rated instrument that measured the participant's overall status on an 11-point numeric rating scale (NRS) ranging from 0 (very poor) to 10 (very good).

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Least Squares Mean

Standard Error

Units on a scale

End of each period, at Weeks 6 and 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo	The below table included participants who received placebo in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). There was a 2-week single-blind taper/washout period between treatment periods.

Other Pre-specified

Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) at Baseline.

C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3) ("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7) ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Number

Participants

Baseline

ID	Title	Description
OG000	Pregabalin/Placebo	Participants were randomized in a 1:1 ratio to double-blind treatment with pregabalin for 6 weeks (3 weeks dose optimization and 3 weeks fixed dose) in period 1 followed by placebo in period 2 with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
OG001	Placebo/Pregabalin

Other Pre-specified

Number of Participants With Categorical Scores on the C-SSRS at Post-Baseline.

C-SSRS assessed whether participant experienced following:completed suicide (1), suicide attempt (2) (response of Yes on "actual attempt"), preparatory acts toward imminent suicidal behavior (3) (Yes on "preparatory acts or behavior"), suicidal ideation (4) (Yes on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (Yes on "Has subject engaged in non-suicidal self-injurious behavior"). Below table indicated one participant (10141023) treated with Pregabalin reported preparatory act. However upon study unblinding it was clarified that preparatory act occurred while the participant was taking placebo. Since preparatory act was reported at first visit of Period 2, by convention statistical summaries classified this under Pregabalin treatment.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Number

Participants

From Visit 3 to Visit 14

ID	Title	Description
OG000	Pregabalin	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.

Other Pre-specified

Work Productivity and Activity Index-Specific Health Problem (WPAI-SHP) Questionnaire at Baseline.

WPAI-SHP assessed work productivity and impairment. It was a participant-rated, six-item questionnaire regarding current employment, hours missed and actually worked, and degree to which a specified health problem affected work productivity and regular activities over the past 7 days. Subscale scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. Each subscale score was expressed as an impairment percentage (0-100) where higher numbers indicated greater impairment and less productivity.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Deviation

Units on a scale

Baseline

ID	Title	Description
OG000	All Participants	All randomized participants were included in this analysis.

Units	Counts
Participants	OG000

Other Pre-specified

Health Utilization Assessment (Total Office Visits, Number of Hospitalizations and Number of Emergency Room Visits) at Baseline.

The healthcare utilization assessment was used to capture healthcare utilization data at Baseline. This assessment contained 10 questions related to aspects of healthcare services.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Deviation

Visits

Baseline

ID	Title	Description
OG000	All Participants	All randomized participants were included in this analysis.

Units	Counts
Participants	OG000

Other Pre-specified

Health Utilization Assessment (Time for Help no Payment) at Baseline.

The healthcare utilization assessment was used to capture healthcare utilization data at Baseline. This assessment contained 10 questions related to aspects of healthcare services. 'Time for help no payment' refers to time other people spent without receiving payment to help with activities the patient cannot perform due to fibromyalgia.

ITT population defined as all participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation.

Posted

Mean

Standard Deviation

Hours

Baseline

ID	Title	Description
OG000	All Participants	All randomized participants were included in this analysis.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Neutrophilia	Blood and lymphatic system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Palpitations	Cardiac disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Dry eye	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0010 affected177 at risk
Eye disorder	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Eyelid oedema	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Vision blurred	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0007 affected181 at risk EG0013 affected177 at risk
Visual impairment	Eye disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0011 affected177 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0013 affected177 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0014 affected177 at risk
Constipation	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG00019 affected181 at risk EG0014 affected177 at risk
Dental caries	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG00016 affected181 at risk EG0017 affected177 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG00012 affected181 at risk EG0011 affected177 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Flatulence	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0012 affected177 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Lip swelling	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Nausea	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG00017 affected181 at risk EG00112 affected177 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Paraesthesia oral	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0010 affected177 at risk
Salivary gland pain	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Toothache	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0015 affected177 at risk
Asthenia	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0012 affected177 at risk
Chest discomfort	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Chest pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0012 affected177 at risk
Crying	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Cyst	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Energy increased	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Fatigue	General disorders	MedDRA 16.0	Non-systematic Assessment	EG00012 affected181 at risk EG0018 affected177 at risk
Feeling abnormal	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected181 at risk EG0010 affected177 at risk
Feeling drunk	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Feeling hot	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Feeling jittery	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Gait disturbance	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0010 affected177 at risk
Hunger	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0011 affected177 at risk
Inflammation	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Irritability	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0011 affected177 at risk
Malaise	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Mucosal dryness	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Non-cardiac chest pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Oedema peripheral	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0007 affected181 at risk EG0013 affected177 at risk
Pain	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Pyrexia	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0014 affected177 at risk
Swelling	General disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Hepatomegaly	Hepatobiliary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Seasonal allergy	Immune system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Bronchitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0012 affected177 at risk
Bronchitis viral	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Cystitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Ear infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0012 affected177 at risk
Folliculitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Gastroenteritis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0013 affected177 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0012 affected177 at risk
Influenza	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0012 affected177 at risk
Laryngitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Nasopharyngitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0005 affected181 at risk EG00110 affected177 at risk
Oral herpes	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Pharyngitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Rhinitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Sinusitis	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0012 affected177 at risk
Tooth infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0012 affected177 at risk
Urinary tract infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0011 affected177 at risk
Vaginal infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Viral infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0012 affected177 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0011 affected177 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0012 affected177 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0010 affected177 at risk
Post concussion syndrome	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Skeletal injury	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Alanine aminotransferase increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Blood glucose increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Blood pressure increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0013 affected177 at risk
Eosinophil count increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Urine output decreased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Weight increased	Investigations	MedDRA 16.0	Non-systematic Assessment	EG00016 affected181 at risk EG0013 affected177 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Folate deficiency	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Food craving	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0010 affected177 at risk
Polydipsia	Metabolism and nutrition disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0012 affected177 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0014 affected177 at risk
Fibromyalgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Medial tibial stress syndrome	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0011 affected177 at risk
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0010 affected177 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0013 affected177 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Amnesia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Areflexia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Balance disorder	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected181 at risk EG0010 affected177 at risk
Burning sensation	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Clumsiness	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Cognitive disorder	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Disturbance in attention	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected181 at risk EG0014 affected177 at risk
Dizziness	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG00051 affected181 at risk EG00112 affected177 at risk
Dizziness postural	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Dysgeusia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Headache	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG00014 affected181 at risk EG00117 affected177 at risk
Hypersomnia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0010 affected177 at risk
Hyporeflexia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Lethargy	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Memory impairment	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected181 at risk EG0011 affected177 at risk
Mental impairment	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Migraine	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0013 affected177 at risk
Myoclonus	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Paraesthesia	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0011 affected177 at risk
Presyncope	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Psychomotor hyperactivity	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Repetitive speech	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Sedation	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0012 affected177 at risk
Somnolence	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG00036 affected181 at risk EG0018 affected177 at risk
Stupor	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Tension headache	Nervous system disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Abnormal dreams	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Anxiety	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0008 affected181 at risk EG0017 affected177 at risk
Apathy	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Bradyphrenia	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Confusional state	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Depressed mood	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0012 affected177 at risk
Depression	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected181 at risk EG0014 affected177 at risk
Disorientation	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0005 affected181 at risk EG0010 affected177 at risk
Euphoric mood	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Initial insomnia	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Insomnia	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG00013 affected181 at risk EG0011 affected177 at risk
Nervousness	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0012 affected177 at risk
Nightmare	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0014 affected177 at risk
Panic attack	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Restlessness	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Sleep disorder	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Thinking abnormal	Psychiatric disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Dysuria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Haematuria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Incontinence	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Oliguria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Urinary retention	Renal and urinary disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Vulvovaginal dryness	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Vulvovaginal pruritus	Reproductive system and breast disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0011 affected177 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0003 affected181 at risk EG0015 affected177 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0010 affected177 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0004 affected181 at risk EG0014 affected177 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0013 affected177 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0010 affected177 at risk
Tooth extraction	Surgical and medical procedures	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Haematoma	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0000 affected181 at risk EG0011 affected177 at risk
Hot flush	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0001 affected181 at risk EG0011 affected177 at risk
Hypertension	Vascular disorders	MedDRA 16.0	Non-systematic Assessment	EG0002 affected181 at risk EG0012 affected177 at risk

ID	Term
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases
D001526	Behavioral Symptoms
D001519	Behavior

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/Placebo	Participants were randomized in a 1:1 ratio to double-blind treatment with pregabalin for 6 weeks (3 weeks dose optimization and 3 weeks fixed dose) in period 1 followed by placebo in period 2 with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
BG001	Placebo/Pregabalin	Participants were randomized in a 1:1 ratio to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (3 weeks dose optimization and 3 weeks fixed dose) with background antidepressants. Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.
BG002	Total	Total of all reporting 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	The below table included participants who received pregabalin in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). Pregabalin was administered as immediate release (IR) capsule with a starting dose of 150 mg/day and increased up to 300 - 450 mg/day during the dose optimization process. There was a 2-week single-blind taper/washout period between treatment periods.			3	181	139	181
EG001	Placebo	The below table included participants who received placebo in either treatment period pooled together due to the crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (3 weeks dose optimization and 3 weeks fixed dose for each treatment period). There was a 2-week single-blind taper/washout period between treatment periods.			1	177	106	177