Trial Outcomes & Findings for An fMRI Study Of Brain Response In Patients With Fibromyalgia (NCT NCT00760474)

Last Updated: 2021-01-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Results posted on

2021-01-22

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Period 1 (P1) STARTED	13	14
Period 1 (P1) Treated	13	14
Period 1 (P1) Overall Number of Unique Participants	12	13
Period 1 (P1) COMPLETED	12	13
Period 1 (P1) NOT COMPLETED	1	1
Placebo Washout Period STARTED	12	13
Placebo Washout Period COMPLETED	12	12
Placebo Washout Period NOT COMPLETED	0	1
Period 2 (P2) STARTED	12	12
Period 2 (P2) COMPLETED	11	11
Period 2 (P2) NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Period 1 (P1) Discontinued then re-entered	1	1
Placebo Washout Period Other	0	1
Period 2 (P2) Lost to Follow-up	1	0
Period 2 (P2) Adverse Event	0	1

Baseline Characteristics

An fMRI Study Of Brain Response In Patients With Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=25 Participants 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.
Age, Continuous	38.6 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex/Gender, Customized	25 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: 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.

Outcome measures

Outcome measures
Measure	Pregabalin n=17 Participants 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.	Placebo n=17 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glu/Cr ratio posterior insula - pre-dose	1.1751 ratio Standard Deviation 0.119537	1.13253 ratio Standard Deviation 0.123897
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glx/Cr ratio anterior insula - pre-dose	1.75888 ratio Standard Deviation 0.164256	1.71671 ratio Standard Deviation 0.203157
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glu/Cr ratio posterior insula - post-dose	1.1046 ratio Standard Deviation 0.14180	1.17129 ratio Standard Deviation 0.151535
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Gln/Cr ratio posterior insula - pre-dose	0.5311 ratio Standard Deviation 0.117359	0.52635 ratio Standard Deviation 0.143649
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Gln/Cr ratio posterior insula - post-dose	0.4857 ratio Standard Deviation 0.14534	0.51553 ratio Standard Deviation 0.147882
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glx/Cr ratio posterior insula - pre-dose	1.70624 ratio Standard Deviation 0.177312	1.65894 ratio Standard Deviation 0.215505
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glx/Cr ratio posterior insula - post-dose	1.5903 ratio Standard Deviation 0.19461	1.68747 ratio Standard Deviation 0.227398
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glu/Cr ratio anterior insula - pre-dose	1.22731 ratio Standard Deviation 0.154333	1.23788 ratio Standard Deviation 0.183282
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glu/Cr ratio anterior insula - post-dose	1.2393 ratio Standard Deviation 0.22290	1.18524 ratio Standard Deviation 0.164847
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Gln/Cr ratio anterior insula - pre-dose	0.53144 ratio Standard Deviation 0.115606	0.47882 ratio Standard Deviation 0.143684
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Gln/Cr ratio anterior insula - post-dose	0.5290 ratio Standard Deviation 0.19367	0.47541 ratio Standard Deviation 0.100247
Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) Glx/Cr ratio anterior insula - post-dose	1.7684 ratio Standard Deviation 0.30019	1.66124 ratio Standard Deviation 0.166421

PRIMARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS. Change from baseline for Period 1 and Period 2 summarized as Least Squares Mean (LS Mean). Abbreviation: Dorso Lateral Prefrontal Cortex (DLPFC).

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=16 Participants 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.	Placebo n=16 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
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 Left (L)_Anterior Insula (anIns)	0.073 percent change Standard Error 0.0378	0.044 percent change Standard Error 0.0378
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 L_Posterior Cingulate	-0.132 percent change Standard Error 0.0414	-0.083 percent change Standard Error 0.0414
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 R_Anterior Insula	0.080 percent change Standard Error 0.0378	0.002 percent change Standard Error 0.0378
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 R_Amygdala	-0.077 percent change Standard Error 0.0572	0.076 percent change Standard Error 0.0572
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 R_BA23_base	0.005 percent change Standard Error 0.0267	-0.017 percent change Standard Error 0.0267
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 R_Insula_base	-0.010 percent change Standard Error 0.0595	0.034 percent change Standard Error 0.0595
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 Anterior Cingulate	0.008 percent change Standard Error 0.0454	-0.024 percent change Standard Error 0.0454
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 Brodman Area (BA) 22	-0.050 percent change Standard Error 0.0709	0.029 percent change Standard Error 0.0709
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 BA40	-0.047 percent change Standard Error 0.0436	0.026 percent change Standard Error 0.0436
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 L_Amygdala	-0.040 percent change Standard Error 0.0502	0.041 percent change Standard Error 0.0502
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 L_Cerebellum	-0.056 percent change Standard Error 0.0317	0.021 percent change Standard Error 0.0317
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 L_DLPFC	-0.002 percent change Standard Error 0.0255	0.023 percent change Standard Error 0.0255
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 L_Mid Insula	-0.011 percent change Standard Error 0.0672	0.100 percent change Standard Error 0.0672
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 L_Mid Temporal Pole	-0.024 percent change Standard Error 0.0307	-0.044 percent change Standard Error 0.0307
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 L_Orbito Front	0.033 percent change Standard Error 0.1000	-0.136 percent change Standard Error 0.1000
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 Periaqueductal gray (PAG)	0.014 percent change Standard Error 0.0351	0.016 percent change Standard Error 0.0351
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 Posterior Insula (pIns)	0.001 percent change Standard Error 0.0294	0.002 percent change Standard Error 0.0294
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 L_Precuneus	-0.057 percent change Standard Error 0.0281	-0.084 percent change Standard Error 0.0281
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 L_Putamen	0.081 percent change Standard Error 0.0347	0.037 percent change Standard Error 0.0347
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 L_Secondary Somatosensory Area (S2)	-0.016 percent change Standard Error 0.0746	0.111 percent change Standard Error 0.0746
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 Right (R)_DLPFC	-0.004 percent change Standard Error 0.0467	0.101 percent change Standard Error 0.0467
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 R_Inferior Parietal Lobule (IPL)_base	-0.042 percent change Standard Error 0.0301	-0.015 percent change Standard Error 0.0301
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 R_Mid Insula	0.015 percent change Standard Error 0.0423	0.028 percent change Standard Error 0.0423
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 R_Mid Front_DLPFC	-0.011 percent change Standard Error 0.0432	0.083 percent change Standard Error 0.0432
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 R_Mid Temporal Pole	-0.048 percent change Standard Error 0.0250	-0.036 percent change Standard Error 0.0250
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 R_Orbito Front	-0.046 percent change Standard Error 0.0709	-0.056 percent change Standard Error 0.0709
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 L_PAG	0.034 percent change Standard Error 0.0349	0.011 percent change Standard Error 0.0349
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 R_Posterior Insula	0.063 percent change Standard Error 0.0345	-0.024 percent change Standard Error 0.0345
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 Posterior Insula	0.050 percent change Standard Error 0.0434	-0.002 percent change Standard Error 0.0434
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 R_Posterior Cingulate	-0.175 percent change Standard Error 0.0476	-0.093 percent change Standard Error 0.0476
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 R_Precuneus	-0.070 percent change Standard Error 0.0332	-0.070 percent change Standard Error 0.0332
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 R_Precuneus_base	-0.040 percent change Standard Error 0.0273	-0.038 percent change Standard Error 0.0273
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 Superior Temporal	-0.039 percent change Standard Error 0.0645	0.026 percent change Standard Error 0.0645
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 R_Premotor	-0.022 percent change Standard Error 0.0415	-0.022 percent change Standard Error 0.0415
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 R_Putamen	0.088 percent change Standard Error 0.0395	0.032 percent change Standard Error 0.0395
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 R_Primary Somatosensory Area (S1)	-0.048 percent change Standard Error 0.0419	0.037 percent change Standard Error 0.0419
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 R_Thalamus	0.010 percent change Standard Error 0.0245	0.018 percent change Standard Error 0.0245
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 Precuneus	-0.066 percent change Standard Error 0.0301	-0.078 percent change Standard Error 0.0301

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=17 Participants 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.	Placebo n=17 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
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 Right (R) anterior mid insula cortex	0.32 percent change in BOLD signal Standard Deviation 0.19	-0.05 percent change in BOLD signal Standard Deviation 0.25
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 Left (L) mid insula cortex	0.23 percent change in BOLD signal Standard Deviation 0.20	0.00 percent change in BOLD signal Standard Deviation 0.21
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 R inferior parietal lobule, Brodman area 40	0.27 percent change in BOLD signal Standard Deviation 0.21	0.05 percent change in BOLD signal Standard Deviation 0.23
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 L inferior parietal lobule, Brodman area 40	0.28 percent change in BOLD signal Standard Deviation 0.27	0.02 percent change in BOLD signal Standard Deviation 0.25
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 Right primary somatosensory cortex	0.14 percent change in BOLD signal Standard Deviation 0.14	-0.01 percent change in BOLD signal Standard Deviation 0.22
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 Left primary somatosensory cortex	0.21 percent change in BOLD signal Standard Deviation 0.18	0.06 percent change in BOLD signal Standard Deviation 0.25
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 Left supplementary motor area	0.02 percent change in BOLD signal Standard Deviation 0.32	0.30 percent change in BOLD signal Standard Deviation 0.34

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: Participants in FAS with quality resting state data (data able to be corrected for motion \[head and cardiorespiratory artifacts\]).

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=14 Participants 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.	Placebo n=14 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_Posterior cingulate (PCC) pre-dose	1.1647 z-score Standard Deviation 1.71738	1.5405 z-score Standard Deviation 1.70926
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_PCC post-dose	2.1504 z-score Standard Deviation 1.87564	1.2409 z-score Standard Deviation 2.29890
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_primary motor region (M1) pre-dose	3.1486 z-score Standard Deviation 3.14585	1.3267 z-score Standard Deviation 1.94564
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_M1 post-dose	3.2605 z-score Standard Deviation 2.80878	1.3771 z-score Standard Deviation 2.01620
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_cerebellum pre-dose	0.3984 z-score Standard Deviation 1.73000	1.4439 z-score Standard Deviation 1.46341
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_cerebellum post-dose	0.0213 z-score Standard Deviation 2.24014	1.0704 z-score Standard Deviation 2.66882
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_Left (L) IPL 3a pre-dose	0.2025 z-score Standard Deviation 1.92233	-0.9296 z-score Standard Deviation 1.50499
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_L IPL 3a post-dose	-0.3792 z-score Standard Deviation 2.18759	-1.2977 z-score Standard Deviation 1.37551
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_L IPL 3b pre-dose	0.6552 z-score Standard Deviation 1.82208	1.7390 z-score Standard Deviation 2.00764
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_L IPL 3b post-dose	1.5614 z-score Standard Deviation 1.58417	0.9930 z-score Standard Deviation 2.50930
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_Right (R) IPL 3b pre-dose	0.8310 z-score Standard Deviation 2.01819	0.7420 z-score Standard Deviation 1.57551
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_R IPL 3b post-dose	0.9766 z-score Standard Deviation 2.52679	0.9081 z-score Standard Deviation 2.18440
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_cuneus pre-dose	2.1363 z-score Standard Deviation 1.97131	1.8543 z-score Standard Deviation 1.85494
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions pIns_cuneus post-dose	3.0410 z-score Standard Deviation 1.84499	2.3324 z-score Standard Deviation 1.84622
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_L IPL pre-dose	2.1404 z-score Standard Deviation 2.21726	1.9982 z-score Standard Deviation 2.40790
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_L IPL post-dose	2.6493 z-score Standard Deviation 2.04040	2.6797 z-score Standard Deviation 2.50765
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_R IPL pre-dose	2.6956 z-score Standard Deviation 2.61359	1.7848 z-score Standard Deviation 2.27345
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_R IPL post-dose	1.2863 z-score Standard Deviation 1.31165	2.6194 z-score Standard Deviation 2.37251
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_S2 pre-dose	1.6592 z-score Standard Deviation 1.69160	1.6799 z-score Standard Deviation 1.64784
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_S2 post-dose	3.1466 z-score Standard Deviation 2.13680	2.4225 z-score Standard Deviation 2.68238
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_cuneus pre-dose	2.5103 z-score Standard Deviation 2.48669	1.7550 z-score Standard Deviation 1.65232
Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions anIns_cuneus post-dose	1.8042 z-score Standard Deviation 2.08443	1.1899 z-score Standard Deviation 1.67701

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Gracely Box Scales for Pain Intensity (GBSint) Including Outliers Minimum pain intensity	4.1184 scores on a scale Standard Error 0.6535	3.4725 scores on a scale Standard Error 0.6535
Gracely Box Scales for Pain Intensity (GBSint) Including Outliers Maximum pain intensity	14.5701 scores on a scale Standard Error 0.6953	15.6117 scores on a scale Standard Error 0.6953

SECONDARY outcome

Timeframe: Baseline/Pre-dose (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Gracely Box Scales for Pain Unpleasantness (GBSunp) Including Outliers Maximum pain unpleasantness	10.1576 scores on a scale Standard Error 0.8294	11.2742 scores on a scale Standard Error 0.8294
Gracely Box Scales for Pain Unpleasantness (GBSunp) Including Outliers Minimum pain unpleasantness	3.3924 scores on a scale Standard Error 0.5803	3.4258 scores on a scale Standard Error 0.5803

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
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	4.1014 scores on a scale Standard Error 0.4104	4.7038 scores on a scale Standard Error 0.4104

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
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	4.3467 scores on a scale Standard Error 0.4436	4.7745 scores on a scale Standard Error 0.4436

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
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	4.3110 scores on a scale Standard Error 0.4787	5.0527 scores on a scale Standard Error 0.4787

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Short-Form McGill Pain Questionnaire (SF-MPQ): Affective Total Score Including Outliers	1.4100 scores on a scale Standard Error 0.3095	1.8173 scores on a scale Standard Error 0.3095

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Short-Form McGill Pain Questionnaire (SF-MPQ): Sensory Total Score Including Outliers	8.6641 scores on a scale Standard Error 1.0759	9.4722 scores on a scale Standard Error 1.0759

SECONDARY outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Short-Form McGill Pain Questionnaire (SF-MPQ): Overall Score Including Outliers	10.0862 scores on a scale Standard Error 1.2657	11.2774 scores on a scale Standard Error 1.2657

SECONDARY outcome

Timeframe: Day 58

Population: FAS; N=number of participants with analyzable data at observation.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=12 Participants 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.	Placebo Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Sphygmomanometry Evoked Allodynia in Relation to the Blood Pressure (BP) Value at Which Allodynia Was Evoked Mean Left Arm BP Cuff Pressure	107.92 mm Hg Standard Deviation 19.837	—
Sphygmomanometry Evoked Allodynia in Relation to the Blood Pressure (BP) Value at Which Allodynia Was Evoked Mean Right Arm BP Cuff Pressure	129.31 mm Hg Standard Deviation 19.917	—

SECONDARY outcome

Timeframe: Day 58

Population: FAS; N=number of participants with analyzable data at observation.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=16 Participants 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.	Placebo Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Pain at the Bilateral Epicondyle Tender Points Assessed Using American College of Rheumatology (ACR) Classification Criteria Pain Severity Left Epicondyle	6.25 scores on a scale Standard Deviation 2.840	—
Pain at the Bilateral Epicondyle Tender Points Assessed Using American College of Rheumatology (ACR) Classification Criteria Pain Severity Right Epicondyle	5.72 scores on a scale Standard Deviation 2.671	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean.

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Hospital Anxiety and Depression Scale (HADS): Anxiety Total Score Including Outliers	4.3896 scores on a scale Standard Error 0.6132	5.1558 scores on a scale Standard Error 0.6132

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Hospital Anxiety and Depression Scale (HADS): Depression Total Score Including Outliers	3.1750 scores on a scale Standard Error 0.4147	3.8705 scores on a scale Standard Error 0.4147

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Pregabalin n=22 Participants 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.	Placebo n=22 Participants Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
Pain Catastrophizing Scale (PCS) Including Outliers	11.4050 scores on a scale Standard Error 1.0192	12.0041 scores on a scale Standard Error 1.0192

Adverse Events

Pregabalin

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pregabalin n=24 participants at risk 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.	Placebo n=25 participants at risk Placebo to match study treatment administered in Period 1 or Placebo to match study treatment administered in Period 2.
General disorders Device material issue	0.00% 0/24 • 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.	4.0% 1/25 • 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.
Nervous system disorders Unresponsive to stimuli	4.2% 1/24 • 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.	0.00% 0/25 • 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.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
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Restriction type: OTHER