A Phase 3b Multicenter Study of Pregabalin in Fibromyalgia Subjects Who Have Comorbid Depression

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.

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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).

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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).

Time frame: Baseline

Population: 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.

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).

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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.

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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.

Time frame: Baseline

Population: 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.

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).

Time frame: Baseline

Population: 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.

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).

Time frame: End of Period 1 at Week 6

Population: 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.

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.

Time frame: Visits 2, 6, and 12

Population: 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.

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.

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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.

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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.

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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.

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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.

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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.

Time frame: Baseline

Population: 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.

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 frame: Baseline

Population: 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.

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).

Time frame: Baseline

Population: 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.

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).

Time frame: End of each period, at Weeks 6 and 14

Population: 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.

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).

Time frame: Baseline

Population: 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.

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.

Time frame: From Visit 3 to Visit 14

Population: 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.

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.

Time frame: End of Period 2 at Week 14

Population: 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.

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.

Time frame: Baseline

Population: 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.