Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Other |
Hospital Anxiety and Depression Scale (HADS): Anxiety Total Score Including Outliers |
A participant rated questionnaire with 2 subscales. HADS-A assessed state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assessed 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 indicated greater severity of anxiety and depression symptoms. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Other |
Hospital Anxiety and Depression Scale (HADS): Depression Total Score Including Outliers |
A participant rated questionnaire with 2 subscales. HADS-A assessed state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assessed 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 indicated greater severity of anxiety and depression symptoms. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Other |
Pain Catastrophizing Scale (PCS) Including Outliers |
PCS is a participant rated 13-item instrument to measure the presence and severity of catastrophizing. Scored 0 (not at all) to 4 (all the time) to statements such as "When I'm in pain…I worry all the time about whether the pain will end". All 13 statements start with "When I'm in pain…". Total score ranged from 0 to 52; higher scores reflected greater impairment. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Primary |
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) |
Single voxel spectra obtained from the anterior and posterior right insula at rest to compare ratios for Gln/Cr, Glu/Cr, and combined Glutamate + Glutamine (Glx/Cr) for pregabalin and placebo. Gln, Glu, Glx calculated as ratios to the internal standard creatine. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Primary |
Voxel-wise Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in Response to Blunt Pressure Pain: Percent Change in BOLD Activations Including Outliers |
BOLD fMRI imaging modality to assess brain activation signals across the whole brain in defined Region of Interest (ROI) brain regions in response to blunt pressure pain; acquired during resting state (no evoked pain) and during evoked pain (thumb pressure device with non-painful pressure, 2 kilograms [kg] pressure/equal stimulus conditions, and high pain pressure/up to 10 kg). Estimated as magnitude (percent change) of the betas representing brain signal activation associated with pressure induced pain. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Voxel-wise Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in Response to a Control Visual (Checkerboard) Stimuli |
BOLD fMRI imaging modality to assess brain activation signals across the whole brain in defined ROI brain regions in response to checkerboard visual stimuli (flashing at 8 hertz [Hz]). Reported as percent change between the pre-dose (baseline) and post-dose values. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions |
Resting state brain activity assessed for correlation of brain seed region (pIns, anIns) to ROI connectivity at baseline (pre-dose) and post-dose (pre minus post) measured using z-score (mean of 0, standard deviation [SD] of 1); range approximately -3 to +3. Positive (+) z-scores reflect greater connectivity (+correlation between seed region and ROI). Negative (-) z-scores reflect -connectivity (anti-correlation between seed region and ROI). ROIs include PCC and IPL from within the default mode network (DMN). DMN is a constellation of regions in which connectivity is augmented in fibromyalgia. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Gracely Box Scales for Pain Intensity (GBSint) Including Outliers |
Minimum and maximum pain intensity acquired during resting state (no evoked pain) and during evoked pain (thumb pressure device with non-painful pressure, 2 kg pressure/equal stimulus conditions, and high pain pressure/up to 10 kg) measured during fMRI and scored from 0 (no pain sensation) to 20 (extremely intense). Baseline and Post-dose data for Period 1 and Period 2 summarized as Least Squares Mean (LS Mean). Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Gracely Box Scales for Pain Unpleasantness (GBSunp) Including Outliers |
Minimum and maximum pain unpleasantness acquired during resting state (no evoked pain) and during evoked pain (thumb pressure device with non-painful pressure, 2 kg pressure/equal stimulus conditions, and high pain pressure/up to 10 kg) measured during fMRI and scored from 0 (neutral) to 20 (very intolerable). Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline/Pre-dose (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Daily Pain Diary Numeric Rating Scale (NRS) Item From the Modified Brief Pain Inventory (mBPI) for Assessment of Clinical Pain: 7 Day Average Pain Score Including Outliers |
The daily pain diary consisted of the mBPI item regarding participant-rated average of pain over the past 24 hours. Scored on an 11-point numeric scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The 7 day average pain score was defined as the mean daily pain NRS value for the last 7 days prior to fMRI scanning visit. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Daily Pain Diary Numeric Rating Scale (NRS) Item From the Modified Brief Pain Inventory (mBPI) for Assessment of Clinical Pain: 3 Day Average Pain Score Including Outliers |
The daily pain diary consisted of the mBPI item regarding participant-rated average of pain over the past 24 hours. Scored on an 11-point numeric scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The 3 day average pain score was defined as the mean daily pain NRS value for the last 3 days prior to fMRI scanning visit. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Daily Pain Diary Numeric Rating Scale (NRS) Item From the Modified Brief Pain Inventory (mBPI) for Assessment of Clinical Pain: Individual Daily Pain Score Including Outliers |
The daily pain diary consisted of the mBPI item regarding participant-rated average of pain over the past 24 hours. Scored on an 11-point numeric scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The individual daily pain score was defined as the final score recorded in the last pain diary of the treatment period 24 hours prior to fMRI scanning visit. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Short-Form McGill Pain Questionnaire (SF-MPQ): Affective Total Score Including Outliers |
SF-MPQ was completed to assess pain over the past week and to assess present pain and consists of 15 pain descriptors: sensory dimension of pain experience (sum of items 1 to 11) and affective dimension (sum of items 12 to 15). Each descriptor was ranked by participant on a 4-point intensity scale (0=none to 3=severe) and totaled in each subclass (sensory range 0 to 33; affective range 0 to 12); higher scores indicated higher pain/impact. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Short-Form McGill Pain Questionnaire (SF-MPQ): Sensory Total Score Including Outliers |
SF-MPQ was completed to assess pain over the past week and to assess present pain and consists of 15 pain descriptors: sensory dimension of pain experience (sum of items 1 to 11) and affective dimension (sum of items 12 to 15). Each descriptor was ranked by participant on a 4-point intensity scale (0=none to 3=severe) and totaled in each subclass (sensory range 0 to 33; affective range 0 to 12); higher scores indicated higher pain/impact. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Short-Form McGill Pain Questionnaire (SF-MPQ): Overall Score Including Outliers |
SF-MPQ was completed to assess pain over the past week and to assess present pain and consists of 15 pain descriptors: sensory dimension of pain experience (sum of items 1 to 11) and affective dimension (sum of items 12 to 15). Each descriptor was ranked by the participant on a 4-point intensity scale (0=none to 3=severe) and totaled in each subclass (sensory range 0 to 33; affective range 0 to 12). Total (overall) score was sum of items 1 to 15, range 0 to 45; higher scores indicated higher pain/impact. Any observation with a studentized residual >3 or <-3 was considered an outlier. |
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
| Secondary |
Sphygmomanometry Evoked Allodynia in Relation to the Blood Pressure (BP) Value at Which Allodynia Was Evoked |
BP cuff evoked allodynia assessed based on participant response to the following question "When I take your blood pressure, tell me if the cuff's pressure is painful". A standard BP cuff was inflated at approximately 10 millimeters of mercury (mm Hg) per second up to 180 mm Hg or to point when participant experienced pain; performed 3 times on each arm whether or not pain was reported. If no pain elicited at 180 mm Hg, it was recorded that no sphygmomanometry-evoked allodynia occurred. If pain was reported, value (in mm Hg) at which pain first occured was recorded for each of the assessments. |
Day 58 |
|
| Secondary |
Pain at the Bilateral Epicondyle Tender Points Assessed Using American College of Rheumatology (ACR) Classification Criteria |
Participant rated severity of pain upon application of 4 kilograms (kg) pressure via dolorimeter at the bilateral epicondyle tender points (2 tender points, 2 centimeters distal to the epicondyles) described in the American College of Rheumatology (ACR) classification criteria and scored on a 0 (no pain) to 10 (worst possible pain) rating scale. Each arm was to be assessed for any pain (one point on each arm) with the application of pressure. |
Day 58 |
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