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The purpose of this study is to explore how pregabalin works in patients with fibromyalgia by evaluating brain imaging signals. To find out whether fMRI (functional magnetic resonance imaging) is an efficient way to show whether new pain medications are effective in treating fibromyalgia.
Methodology study
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pregabalin, then placebo | Experimental |
| |
| Placebo, then pregabalin | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pregabalin, then placebo | Drug | Placebo and pregabalin will be given orally twice daily in capsules at different times during the course of the study. The highest dose of pregabalin to be used in the study is 450 mg/day. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | Ann Arbor | Michigan | 48106 | United States | ||
| Pfizer Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33982890 | Derived | Ichesco E, Peltier SJ, Mawla I, Harper DE, Pauer L, Harte SE, Clauw DJ, Harris RE. Prediction of Differential Pharmacologic Response in Chronic Pain Using Functional Neuroimaging Biomarkers and a Support Vector Machine Algorithm: An Exploratory Study. Arthritis Rheumatol. 2021 Nov;73(11):2127-2137. doi: 10.1002/art.41781. Epub 2021 Sep 22. | |
| 26816332 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Participants who met entrance criteria received placebo for 1 week (Day 1 to 8) then were randomized in a 1:1 ratio to blinded treatment sequence.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pregabalin First, Then Placebo | Pregabalin 75 milligrams (mg) by mouth (PO) twice daily (BID) Period 1/Day 9 to 11; 150 mg BID Day 12 to 16; 200 mg BID Day 17 to 19; 225 mg BID Day 20 to 22 followed by taper Day 23 to 29 and an 8-day placebo washout period. Then, placebo matching study treatment in a similar pattern was administered beginning Period 2/Day 38. |
| FG001 | Placebo First, Then Pregabalin | Placebo matching study treatment was administered beginning Period 1/Day9. Then, Pregabalin 75 mg BID Period 2/Day 38 to 40; 150 mg BID Day 41 to 45; 200 mg BID Day 46 to 48; 225 mg BID Day 49 to 51 followed by placebo taper Day 52 to 58. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (P1) |
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| Placebo Washout Period |
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| Period 2 (P2) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | Participants who met entrance criteria received placebo for 1 week (Day 1 to 8) then were randomized in a 1:1 ratio to blinded treatment sequence to receive either: Pregabalin, then placebo: Pregabalin 75 mg PO BID Period 1/Day 9 to 11; 150 mg BID Day 12 to 16; 200 mg BID Day 17 to 19; 225 mg BID Day 20 to 22 followed by taper Day 23 to 29 and an 8-day placebo washout period. Then, placebo matching study treatment in a similar pattern was administered beginning Period 2/Day 38 and included dose escalation through Day 51 followed by placebo taper Day 52 to 58. Or placebo, then Pregabalin: Placebo matching study treatment was administered in a similar fashion to Pregabalin treatment beginning Period 1/Day 9 and included dose escalation, taper and an 8-day placebo washout period. Then, Pregabalin 75 mg BID Period 2/Day 38 to 40; 150 mg BID Day 41 to 45; 200 mg BID Day 46 to 48; 225 mg BID Day 49 to 51 followed by placebo taper Day 52 to 58. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 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. | Full Analysis Set (FAS) all participants who received a minimum fixed dose of 300 mg/day of study treatment. N=number of participants with analyzable data at observation. | Posted | Mean | Standard Deviation | ratio | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
|
Treatment emergent adverse events (all causalities) were reported from the time of first dose of study treatment up to 28 days after last dose of study treatment.
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pregabalin | Pregabalin administered in Period 1 (75 mg BID Period 1/Day 9 to 11; then 150 mg BID Period 1/Day 12 to 16; then 200 mg BID Period 1/Day 17 to 19; then 225 mg BID Period 1/Day 20 to 22) or administered in Period 2 (75 mg BID Period 2/Day 38 to 40; then 150 mg BID Period 2/Day 41 to 45; then 200 mg BID Period 2/Day 46 to 48; then 225 mg BID Period 2/Day 49 to 51); then taper Period 2/Day 52 to 58. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Device material issue | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.govCallCenter@pfizer.com |
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| ID | Term |
|---|---|
| D005356 | Fibromyalgia |
| D010146 | Pain |
| ID | Term |
|---|---|
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009468 | Neuromuscular Diseases |
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| ID | Term |
|---|---|
| D000069583 | Pregabalin |
| ID | Term |
|---|---|
| D005680 | gamma-Aminobutyric Acid |
| D000613 | Aminobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
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| Placebo, then pregabalin | Drug | Placebo and pregabalin will be given orally twice daily in capsules at different times during the course of the study. The highest dose of pregabalin to be used in the study is 450 mg/day. |
|
| Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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 |
| 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 |
| Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
| 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) |
| 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) |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| Puiu T, Kairys AE, Pauer L, Schmidt-Wilcke T, Ichesco E, Hampson JP, Napadow V, Clauw DJ, Harris RE. Association of Alterations in Gray Matter Volume With Reduced Evoked-Pain Connectivity Following Short-Term Administration of Pregabalin in Patients With Fibromyalgia. Arthritis Rheumatol. 2016 Jun;68(6):1511-21. doi: 10.1002/art.39600. |
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| Sex/Gender, Customized | Female | Number | participants |
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| OG001 | Placebo | Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2. |
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| 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. | FAS. Change from baseline for Period 1 and Period 2 summarized as Least Squares Mean (LS Mean). Abbreviation: Dorso Lateral Prefrontal Cortex (DLPFC). | Posted | Least Squares Mean | Standard Error | percent change | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS. | Posted | Mean | Standard Deviation | percent change in BOLD signal | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | Participants in FAS with quality resting state data (data able to be corrected for motion [head and cardiorespiratory artifacts]). | Posted | Mean | Standard Deviation | z-score | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline/Pre-dose (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| Other Pre-specified | 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. | FAS. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| Other Pre-specified | 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. | FAS. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| Other Pre-specified | 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. | FAS | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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|
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| 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. | FAS. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) |
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| 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. | FAS; N=number of participants with analyzable data at observation. | Posted | Mean | Standard Deviation | mm Hg | Day 58 |
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| 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. | FAS; N=number of participants with analyzable data at observation. | Posted | Mean | Standard Deviation | scores on a scale | Day 58 |
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| 1 |
| 24 |
| 18 |
| 24 |
| EG001 | Placebo | Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2. | 1 | 25 | 13 | 25 |
| Unresponsive to stimuli | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Chest discomfort | General disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Facial pain | General disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Feeling jittery | General disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (14.0) | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
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| Blood calcium increased | Investigations | MedDRA (14.0) | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Fibromyalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Myalgia | Metabolism and nutrition disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Non-systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Euphoric mood | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
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Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D009422 |
| Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| BA40 |
|
| Left (L)_Anterior Insula (anIns) |
|
| L_Amygdala |
|
| L_Cerebellum |
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| L_DLPFC |
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| L_Mid Insula |
|
| L_Mid Temporal Pole |
|
| L_Orbito Front |
|
| Periaqueductal gray (PAG) |
|
| Posterior Insula (pIns) |
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| L_Posterior Cingulate |
|
| L_Precuneus |
|
| L_Putamen |
|
| L_Secondary Somatosensory Area (S2) |
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| Right (R)_DLPFC |
|
| R_Anterior Insula |
|
| R_Amygdala |
|
| R_BA23_base |
|
| R_Inferior Parietal Lobule (IPL)_base |
|
| R_Insula_base |
|
| R_Mid Insula |
|
| R_Mid Front_DLPFC |
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| R_Mid Temporal Pole |
|
| R_Orbito Front |
|
| L_PAG |
|
| R_Posterior Insula |
|
| Posterior Insula |
|
| R_Posterior Cingulate |
|
| R_Precuneus |
|
| R_Precuneus_base |
|
| Superior Temporal |
|
| R_Premotor |
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| R_Putamen |
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| R_Primary Somatosensory Area (S1) |
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| R_Thalamus |
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| Precuneus |
|
BA22 |
| Mixed Models Analysis |
Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. |
| 0.5181 |
Significance was set at p <0.05. |
| Least Squares (LS) Mean difference |
| -0.079 |
| 2-Sided |
| 95 |
| -0.3356 |
| 0.1771 |
| Superiority or Other (legacy) |
| BA40 | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.2987 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.072 | 2-Sided | 95 | -0.2161 | 0.0714 | Superiority or Other (legacy) |
| L_anIns | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.5151 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.029 | 2-Sided | 95 | -0.0640 | 0.1219 | Superiority or Other (legacy) |
| L_Amygdala | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.2369 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.081 | 2-Sided | 95 | -0.2228 | 0.0599 | Superiority or Other (legacy) |
| L_Cerebellum | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.0758 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.077 | 2-Sided | 95 | -0.1642 | 0.0092 | Superiority or Other (legacy) |
| L_DLPFC | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.4609 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.025 | 2-Sided | 95 | -0.0947 | 0.0452 | Superiority or Other (legacy) |
| L_Mid Insula | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.3813 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.111 | 2-Sided | 95 | -0.3745 | 0.1524 | Superiority or Other (legacy) |
| L_Mid Temporal Pole | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.7200 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.020 | 2-Sided | 95 | -0.0964 | 0.1361 | Superiority or Other (legacy) |
| L_Orbito Front | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.2099 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.168 | 2-Sided | 95 | -0.1065 | 0.4434 | Superiority or Other (legacy) |
| PAG | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.9551 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.003 | 2-Sided | 95 | -0.1047 | 0.0992 | Superiority or Other (legacy) |
| Posterior Insula | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.9940 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.000 | 2-Sided | 95 | -0.0855 | 0.0848 | Superiority or Other (legacy) |
| L_Posterior Cingulate | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.4291 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.049 | 2-Sided | 95 | -0.1792 | 0.0806 | Superiority or Other (legacy) |
| L_Precuneus | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.4670 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.027 | 2-Sided | 95 | -0.0496 | 0.1028 | Superiority or Other (legacy) |
| L_Putamen | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.4443 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.044 | 2-Sided | 95 | -0.0752 | 0.1624 | Superiority or Other (legacy) |
| L_S2 | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.2823 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.127 | 2-Sided | 95 | -0.3704 | 0.1165 | Superiority or Other (legacy) |
| R_DLPFC | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.1369 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.105 | 2-Sided | 95 | -0.2481 | 0.0378 | Superiority or Other (legacy) |
| R_anIns | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.2376 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.078 | 2-Sided | 95 | -0.0573 | 0.2127 | Superiority or Other (legacy) |
| R_Amygdala | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.0968 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.153 | 2-Sided | 95 | -0.3365 | 0.0313 | Superiority or Other (legacy) |
| R_BA23_base | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.5720 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.023 | 2-Sided | 95 | -0.0610 | 0.1062 | Superiority or Other (legacy) |
| R_IPL_base | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.5822 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.027 | 2-Sided | 95 | -0.1303 | 0.0761 | Superiority or Other (legacy) |
| R_Insula_base | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.6851 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.044 | 2-Sided | 95 | -0.2697 | 0.1824 | Superiority or Other (legacy) |
| R_Mid Insula | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.8656 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.013 | 2-Sided | 95 | -0.1699 | 0.1446 | Superiority or Other (legacy) |
| R_Mid Front_DLPFC | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.1562 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.094 | 2-Sided | 95 | -0.2296 | 0.0407 | Superiority or Other (legacy) |
| R_Mid Temporal Pole | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.7752 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.012 | 2-Sided | 95 | -0.0991 | 0.0754 | Superiority or Other (legacy) |
| R_Orbito Front | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.9182 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.010 | 2-Sided | 95 | -0.1912 | 0.2109 | Superiority or Other (legacy) |
| L_PAG | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.6544 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.022 | 2-Sided | 95 | -0.0829 | 0.1278 | Superiority or Other (legacy) |
| R_pIns | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.0813 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.087 | 2-Sided | 95 | -0.0123 | 0.1863 | Superiority or Other (legacy) |
| R_pIns | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.4605 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.052 | 2-Sided | 95 | -0.0956 | 0.2004 | Superiority or Other (legacy) |
| R_Posterior Cingulate | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.3136 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.081 | 2-Sided | 95 | -0.2484 | 0.0856 | Superiority or Other (legacy) |
| R_Precuneus | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.9929 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.000 | 2-Sided | 95 | -0.0885 | 0.0893 | Superiority or Other (legacy) |
| R_Precuneus_base | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.9490 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.002 | 2-Sided | 95 | -0.0815 | 0.0767 | Superiority or Other (legacy) |
| Superior Temporal | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.5668 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.065 | 2-Sided | 95 | -0.3019 | 0.1722 | Superiority or Other (legacy) |
| R_Premotor | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.9958 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.000 | 2-Sided | 95 | -0.1398 | 0.1391 | Superiority or Other (legacy) |
| R_Putamen | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.3379 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.057 | 2-Sided | 95 | -0.0659 | 0.1795 | Superiority or Other (legacy) |
| R_S1 | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.2186 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.085 | 2-Sided | 95 | -0.2262 | 0.0565 | Superiority or Other (legacy) |
| R_Thalamus | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.8191 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | -0.008 | 2-Sided | 95 | -0.0843 | 0.0678 | Superiority or Other (legacy) |
| Precuneus | Mixed Models Analysis | Mixed-effect repeated measure model included participant as a random effect; treatment, visit as fixed effects. | 0.7647 | Significance was set at p <0.05. | Least Squares (LS) Mean difference | 0.012 | 2-Sided | 95 | -0.0698 | 0.0930 | Superiority or Other (legacy) |
| R inferior parietal lobule, Brodman area 40 |
|
| L inferior parietal lobule, Brodman area 40 |
|
| Right primary somatosensory cortex |
|
| Left primary somatosensory cortex |
|
| Left supplementary motor area |
|
| pIns_primary motor region (M1) pre-dose |
|
| pIns_M1 post-dose |
|
| pIns_cerebellum pre-dose |
|
| pIns_cerebellum post-dose |
|
| pIns_Left (L) IPL 3a pre-dose |
|
| pIns_L IPL 3a post-dose |
|
| pIns_L IPL 3b pre-dose |
|
| pIns_L IPL 3b post-dose |
|
| pIns_Right (R) IPL 3b pre-dose |
|
| pIns_R IPL 3b post-dose |
|
| pIns_cuneus pre-dose |
|
| pIns_cuneus post-dose |
|
| anIns_L IPL pre-dose |
|
| anIns_L IPL post-dose |
|
| anIns_R IPL pre-dose |
|
| anIns_R IPL post-dose |
|
| anIns_S2 pre-dose |
|
| anIns_S2 post-dose |
|
| anIns_cuneus pre-dose |
|
| anIns_cuneus post-dose |
|