Trial Outcomes & Findings for An Open-Label Comparison of Duloxetine to Other Alternatives for the Management of Diabetic Peripheral Neuropathic Pain (NCT NCT00385671)

Results Overview

This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Data presented represent the weekly mean of the scores of the average pain severity over the last 24 hours. Scores are based on daily assessments recorded by patients in their diaries. Least-squares means represent adjustment due to baseline severity and investigative site.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

407 participants

Primary outcome timeframe

baseline, 12 weeks

Results posted on

2011-07-26

Participant Flow

Participant milestones

Participant milestones
Measure	Pregabalin Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Overall Study STARTED	134	138	135
Overall Study COMPLETED	96	87	99
Overall Study NOT COMPLETED	38	51	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Overall Study Adverse Event	14	27	18
Overall Study Lack of Efficacy	5	9	5
Overall Study Lost to Follow-up	6	6	5
Overall Study Physician Decision	2	1	2
Overall Study Protocol Violation	5	2	1
Overall Study Sponsor Decision	2	2	1
Overall Study Withdrawal by Subject	4	4	4

Baseline Characteristics

An Open-Label Comparison of Duloxetine to Other Alternatives for the Management of Diabetic Peripheral Neuropathic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin n=134 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.	Total n=407 Participants Total of all reporting groups
Age Continuous	61.89 years STANDARD_DEVIATION 10.70 • n=5 Participants	60.94 years STANDARD_DEVIATION 10.18 • n=7 Participants	61.85 years STANDARD_DEVIATION 10.84 • n=5 Participants	61.56 years STANDARD_DEVIATION 10.56 • n=4 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	55 Participants n=7 Participants	52 Participants n=5 Participants	165 Participants n=4 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	83 Participants n=7 Participants	83 Participants n=5 Participants	242 Participants n=4 Participants
Race/Ethnicity, Customized Native American	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized East Asian	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized Hispanic	9 participants n=5 Participants	15 participants n=7 Participants	9 participants n=5 Participants	33 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	13 participants n=5 Participants	9 participants n=7 Participants	11 participants n=5 Participants	33 participants n=4 Participants
Race/Ethnicity, Customized White	111 participants n=5 Participants	110 participants n=7 Participants	112 participants n=5 Participants	333 participants n=4 Participants
Race/Ethnicity, Customized West Asian	0 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Region of Enrollment United States	104 participants n=5 Participants	112 participants n=7 Participants	109 participants n=5 Participants	325 participants n=4 Participants
Region of Enrollment Germany	22 participants n=5 Participants	20 participants n=7 Participants	21 participants n=5 Participants	63 participants n=4 Participants
Region of Enrollment Canada	5 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	12 participants n=4 Participants
Region of Enrollment Puerto Rico	3 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	7 participants n=4 Participants
Duration of Diabetes	150.26 months STANDARD_DEVIATION 131.60 • n=5 Participants	147.14 months STANDARD_DEVIATION 116.04 • n=7 Participants	119.82 months STANDARD_DEVIATION 93.38 • n=5 Participants	139.09 months STANDARD_DEVIATION 115.24 • n=4 Participants
Duration of Diabetic Peripheral Neuropathic Pain	51.54 months STANDARD_DEVIATION 40.96 • n=5 Participants	58.08 months STANDARD_DEVIATION 57.57 • n=7 Participants	50.32 months STANDARD_DEVIATION 41.93 • n=5 Participants	53.34 months STANDARD_DEVIATION 47.51 • n=4 Participants
Michigan Neuropathy Screening Instrument (MNSI) Physical Assessment - Total Score	5.91 units on a scale STANDARD_DEVIATION 1.56 • n=5 Participants	5.73 units on a scale STANDARD_DEVIATION 1.58 • n=7 Participants	5.94 units on a scale STANDARD_DEVIATION 1.56 • n=5 Participants	5.86 units on a scale STANDARD_DEVIATION 1.56 • n=4 Participants
Types of Diabetes Mellitus Type I	13 participants n=5 Participants	9 participants n=7 Participants	9 participants n=5 Participants	31 participants n=4 Participants
Types of Diabetes Mellitus Type II	121 participants n=5 Participants	129 participants n=7 Participants	126 participants n=5 Participants	376 participants n=4 Participants
Weekly mean of 24 hour average pain severity	5.69 units on a scale STANDARD_DEVIATION 1.43 • n=5 Participants	5.81 units on a scale STANDARD_DEVIATION 1.51 • n=7 Participants	5.78 units on a scale STANDARD_DEVIATION 1.47 • n=5 Participants	5.76 units on a scale STANDARD_DEVIATION 1.47 • n=4 Participants
Beck Depression Inventory (BDI) Total Score	9.45 units on a scale STANDARD_DEVIATION 8.53 • n=5 Participants	9.10 units on a scale STANDARD_DEVIATION 7.20 • n=7 Participants	10.71 units on a scale STANDARD_DEVIATION 8.42 • n=5 Participants	9.74 units on a scale STANDARD_DEVIATION 8.07 • n=4 Participants
Weekly mean of the daily worst pain severity	6.92 units on a scale STANDARD_DEVIATION 1.56 • n=5 Participants	7.12 units on a scale STANDARD_DEVIATION 1.46 • n=7 Participants	7.05 units on a scale STANDARD_DEVIATION 1.48 • n=5 Participants	7.03 units on a scale STANDARD_DEVIATION 1.50 • n=4 Participants
Weekly mean of nighttime pain severity	5.64 units on a scale STANDARD_DEVIATION 2.06 • n=5 Participants	5.86 units on a scale STANDARD_DEVIATION 1.74 • n=7 Participants	5.55 units on a scale STANDARD_DEVIATION 2.11 • n=5 Participants	5.69 units on a scale STANDARD_DEVIATION 1.97 • n=4 Participants
Leeds Sleep Evaluation Questionnaire (LSEQ) Awakening Subscale	93.95 units on a scale STANDARD_DEVIATION 41.55 • n=5 Participants	88.63 units on a scale STANDARD_DEVIATION 40.75 • n=7 Participants	86.70 units on a scale STANDARD_DEVIATION 42.46 • n=5 Participants	89.75 units on a scale STANDARD_DEVIATION 41.59 • n=4 Participants
Leeds Sleep Evaluation Questionnaire (LSEQ) Behavior Following Wakefulness Subscale	132.22 units on a scale STANDARD_DEVIATION 69.22 • n=5 Participants	128.87 units on a scale STANDARD_DEVIATION 65.53 • n=7 Participants	131.55 units on a scale STANDARD_DEVIATION 69.61 • n=5 Participants	130.88 units on a scale STANDARD_DEVIATION 67.98 • n=4 Participants
Leeds Sleep Evaluation Questionnaire (LSEQ) Getting to Sleep Subscale	138.62 units on a scale STANDARD_DEVIATION 59.68 • n=5 Participants	137.61 units on a scale STANDARD_DEVIATION 62.91 • n=7 Participants	145.22 units on a scale STANDARD_DEVIATION 64.73 • n=5 Participants	140.45 units on a scale STANDARD_DEVIATION 62.40 • n=4 Participants
Leeds Sleep Evaluation Questionnaire (LSEQ) Quality of Sleep Subscale	95.54 units on a scale STANDARD_DEVIATION 44.08 • n=5 Participants	95.89 units on a scale STANDARD_DEVIATION 46.82 • n=7 Participants	97.01 units on a scale STANDARD_DEVIATION 45.39 • n=5 Participants	96.15 units on a scale STANDARD_DEVIATION 45.34 • n=4 Participants
Sheehan Disability Scale (SDS) Global Functional Impairment Total Score	11.44 units on a scale STANDARD_DEVIATION 8.72 • n=5 Participants	13.49 units on a scale STANDARD_DEVIATION 9.00 • n=7 Participants	12.69 units on a scale STANDARD_DEVIATION 7.92 • n=5 Participants	12.55 units on a scale STANDARD_DEVIATION 8.58 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) male participants - total	40.41 units on a scale STANDARD_DEVIATION 9.01 • n=5 Participants	38.81 units on a scale STANDARD_DEVIATION 9.50 • n=7 Participants	39.25 units on a scale STANDARD_DEVIATION 9.75 • n=5 Participants	39.46 units on a scale STANDARD_DEVIATION 9.42 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) female participants - total	35.21 units on a scale STANDARD_DEVIATION 11.68 • n=5 Participants	36.69 units on a scale STANDARD_DEVIATION 10.43 • n=7 Participants	34.45 units on a scale STANDARD_DEVIATION 10.09 • n=5 Participants	35.43 units on a scale STANDARD_DEVIATION 10.73 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) male participants - arousal	7.19 units on a scale STANDARD_DEVIATION 3.08 • n=5 Participants	6.35 units on a scale STANDARD_DEVIATION 2.88 • n=7 Participants	6.41 units on a scale STANDARD_DEVIATION 3.12 • n=5 Participants	6.64 units on a scale STANDARD_DEVIATION 3.04 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) female participants - arousal	6.64 units on a scale STANDARD_DEVIATION 3.20 • n=5 Participants	7.00 units on a scale STANDARD_DEVIATION 2.72 • n=7 Participants	6.47 units on a scale STANDARD_DEVIATION 3.09 • n=5 Participants	6.70 units on a scale STANDARD_DEVIATION 3.01 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) male participants - desire/frequency	5.32 units on a scale STANDARD_DEVIATION 1.73 • n=5 Participants	5.09 units on a scale STANDARD_DEVIATION 1.77 • n=7 Participants	5.15 units on a scale STANDARD_DEVIATION 1.96 • n=5 Participants	5.18 units on a scale STANDARD_DEVIATION 1.82 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) female participants - desire/frequency	3.79 units on a scale STANDARD_DEVIATION 1.85 • n=5 Participants	4.27 units on a scale STANDARD_DEVIATION 1.83 • n=7 Participants	3.74 units on a scale STANDARD_DEVIATION 1.59 • n=5 Participants	3.93 units on a scale STANDARD_DEVIATION 1.77 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) male participants - desire/interest	7.71 units on a scale STANDARD_DEVIATION 2.56 • n=5 Participants	7.91 units on a scale STANDARD_DEVIATION 2.72 • n=7 Participants	8.06 units on a scale STANDARD_DEVIATION 2.84 • n=5 Participants	7.90 units on a scale STANDARD_DEVIATION 2.71 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) female participants - desire/interest	5.96 units on a scale STANDARD_DEVIATION 3.01 • n=5 Participants	5.97 units on a scale STANDARD_DEVIATION 2.42 • n=7 Participants	5.72 units on a scale STANDARD_DEVIATION 2.43 • n=5 Participants	5.89 units on a scale STANDARD_DEVIATION 2.63 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) male participants - orgasm	7.77 units on a scale STANDARD_DEVIATION 2.93 • n=5 Participants	7.21 units on a scale STANDARD_DEVIATION 2.85 • n=7 Participants	7.51 units on a scale STANDARD_DEVIATION 3.06 • n=5 Participants	7.49 units on a scale STANDARD_DEVIATION 2.94 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) female participants - orgasm	6.98 units on a scale STANDARD_DEVIATION 3.75 • n=5 Participants	8.23 units on a scale STANDARD_DEVIATION 3.94 • n=7 Participants	7.53 units on a scale STANDARD_DEVIATION 3.83 • n=5 Participants	7.56 units on a scale STANDARD_DEVIATION 3.84 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) male participants - pleasure	2.43 units on a scale STANDARD_DEVIATION 1.23 • n=5 Participants	2.50 units on a scale STANDARD_DEVIATION 1.22 • n=7 Participants	2.30 units on a scale STANDARD_DEVIATION 1.11 • n=5 Participants	2.41 units on a scale STANDARD_DEVIATION 1.19 • n=4 Participants
Clayton Sexual Functioning Questionnaire (CSFQ) female participants - pleasure	2.06 units on a scale STANDARD_DEVIATION 1.19 • n=5 Participants	2.23 units on a scale STANDARD_DEVIATION 1.18 • n=7 Participants	2.06 units on a scale STANDARD_DEVIATION 1.13 • n=5 Participants	2.12 units on a scale STANDARD_DEVIATION 1.16 • n=4 Participants
Comorbidity with Generalized Anxiety Disorder (GAD) Yes	3 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	4 participants n=4 Participants
Comorbidity with Generalized Anxiety Disorder (GAD) No	131 participants n=5 Participants	138 participants n=7 Participants	134 participants n=5 Participants	403 participants n=4 Participants
Comorbidity with Major Depressive Disorder (MDD) Yes	4 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Comorbidity with Major Depressive Disorder (MDD) No	130 participants n=5 Participants	135 participants n=7 Participants	131 participants n=5 Participants	396 participants n=4 Participants

PRIMARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Data presented represent the weekly mean of the scores of the average pain severity over the last 24 hours. Scores are based on daily assessments recorded by patients in their diaries. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=93 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=77 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Weekly Mean of Daily 24 Hour Average Pain Score, Pregabalin Compared With Duloxetine	-2.12 units on a scale Standard Error 0.19	-2.62 units on a scale Standard Error 0.21	—

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Data presented represent the weekly mean of the scores of the average pain severity over the last 24 hours. Scores are based on daily assessments recorded by patients in their diaries. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=86 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=77 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Weekly Mean of Daily 24 Hour Average Pain Score, Duloxetine Compared With Duloxetine+Gabapentin	-2.39 units on a scale Standard Error 0.20	-2.62 units on a scale Standard Error 0.21	—

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Data presented represent the weekly mean of the scores of the daily nighttime pain severity over the last 24 hours. Scores are based on daily assessments recorded by patients in their diaries. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=120 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Weekly Mean of Nighttime Pain Severity	-2.30 units on a scale Standard Error 0.21	-2.71 units on a scale Standard Error 0.22	-2.49 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Data presented represent the weekly mean of the scores of the daily worst pain severity over the last 24 hours. Scores are based on daily assessments recorded by patients in their diaries. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=120 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Weekly Mean of the Daily Worst Pain Severity Score	-2.59 units on a scale Standard Error 0.22	-3.08 units on a scale Standard Error 0.24	-2.86 units on a scale Standard Error 0.23

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=117 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=125 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=120 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Clinical Global Impression of Severity Scale (CGI Severity) baseline	4.27 units on a scale Standard Error 0.85	4.47 units on a scale Standard Error 0.90	4.40 units on a scale Standard Error 0.79
Mean Change From Baseline to 12 Weeks in Clinical Global Impression of Severity Scale (CGI Severity) change	-1.06 units on a scale Standard Error 0.10	-1.16 units on a scale Standard Error 0.10	-1.13 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Pregabalin n=122 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=125 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=121 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Patient's Global Impression of Improvement Scale (PGI - Improvement) at 12 Weeks	3.03 units on a scale Standard Deviation 1.19	3.01 units on a scale Standard Deviation 1.68	2.83 units on a scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: 24-hour Average Pain baseline	5.53 units on a scale Standard Error 1.87	5.65 units on a scale Standard Error 1.72	5.75 units on a scale Standard Error 1.76
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: 24-hour Average Pain change	-1.80 units on a scale Standard Error 0.20	-2.44 units on a scale Standard Error 0.21	-2.29 units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: baseline, 12 Weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the severity of pain based on the worst pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Worst Pain baseline	6.73 units on a scale Standard Error 2.01	6.87 units on a scale Standard Error 2.06	7.00 units on a scale Standard Error 1.83
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Worst Pain change	-2.34 units on a scale Standard Error 0.23	-3.02 units on a scale Standard Error 0.25	-2.64 units on a scale Standard Error 0.23

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the severity of pain based on the least pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Least Pain baseline	4.23 units on a scale Standard Error 2.28	4.18 units on a scale Standard Error 2.11	4.07 units on a scale Standard Error 2.14
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Least Pain change	-1.27 units on a scale Standard Error 0.19	-1.55 units on a scale Standard Error 0.20	-1.54 units on a scale Standard Error 0.19

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the severity of pain based on the pain right now. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Pain Right Now baseline	4.98 units on a scale Standard Error 2.33	5.03 units on a scale Standard Error 2.30	5.36 units on a scale Standard Error 2.18
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Severity: Pain Right Now change	-1.77 units on a scale Standard Error 0.21	-2.24 units on a scale Standard Error 0.22	-2.19 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the interference of pain in the past 24 hours on general activity. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference: With General Activity baseline	4.24 units on a scale Standard Error 2.67	5.03 units on a scale Standard Error 2.65	5.03 units on a scale Standard Error 2.48
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference: With General Activity change	-1.51 units on a scale Standard Error 0.22	-2.38 units on a scale Standard Error 0.23	-1.86 units on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the interference of pain in the past 24 hours on mood. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Mood baseline	3.42 units on a scale Standard Error 2.73	4.08 units on a scale Standard Error 2.66	4.10 units on a scale Standard Error 2.67
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Mood change	-1.46 units on a scale Standard Error 0.21	-1.85 units on a scale Standard Error 0.23	-1.43 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the interference of pain in the past 24 hours on walking ability. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Walking Ability baseline	5.25 units on a scale Standard Error 2.72	5.52 units on a scale Standard Error 2.85	5.79 units on a scale Standard Error 2.53
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Walking Ability change	-1.88 units on a scale Standard Error 0.24	-2.56 units on a scale Standard Error 0.26	-2.09 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the interference of pain in the past 24 hours on normal work. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Normal Work baseline	4.61 units on a scale Standard Error 2.86	4.98 units on a scale Standard Error 2.86	5.15 units on a scale Standard Error 2.54
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Normal Work change	-1.63 units on a scale Standard Error 0.24	-1.86 units on a scale Standard Error 0.25	-1.88 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the interference of pain in the past 24 hours on relations with other people. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Relations With Other People baseline	2.96 units on a scale Standard Error 2.68	3.08 units on a scale Standard Error 2.72	3.29 units on a scale Standard Error 2.58
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Relations With Other People change	-0.97 units on a scale Standard Error 0.21	-1.27 units on a scale Standard Error 0.22	-1.17 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the interference of pain in the past 24 hours on sleep. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Sleep baseline	4.91 units on a scale Standard Error 2.87	4.97 units on a scale Standard Error 2.94	5.40 units on a scale Standard Error 2.81
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Sleep change	-2.29 units on a scale Standard Error 0.24	-2.12 units on a scale Standard Error 0.26	-2.50 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A self-reported scale that measures the interference of pain in the past 24 hours on enjoyment of life. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Enjoyment of Life baseline	4.38 units on a scale Standard Error 3.08	4.63 units on a scale Standard Error 2.96	5.02 units on a scale Standard Error 2.68
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Interference With Enjoyment of Life change	-1.82 units on a scale Standard Error 0.22	-2.09 units on a scale Standard Error 0.24	-2.33 units on a scale Standard Error 0.23

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=128 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=130 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=126 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Mean Interference Score baseline	4.25 units on a scale Standard Error 2.34	4.61 units on a scale Standard Error 2.36	4.83 units on a scale Standard Error 2.13
Mean Change From Baseline to 12 Weeks in Brief Pain Inventory (BPI) - Mean Interference Score change	-1.62 units on a scale Standard Error 0.20	-2.00 units on a scale Standard Error 0.21	-1.90 units on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is a nominal outcome reflecting whether or not a clinically-important efficacy outcome was achieved at endpoint. It is based on a comparison between baseline and endpoint scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by patients in their diaries.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=120 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Number of Participants With ≥ 30% Reduction in the Weekly Mean 24 Hour Average Pain Score at 12 Weeks	65 participants	68 participants	72 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is a nominal outcome reflecting whether or not a clinically-important efficacy outcome was achieved at endpoint. It is based on a comparison between baseline and endpoint scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by patients in their diaries.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=120 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Number of Patients With a Reduction of ≥ 50% in Weekly Mean of 24 Hour Average Pain Score	48 participants	50 participants	47 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is a nominal outcome reflecting whether or not a clinically-important efficacy outcome was achieved at endpoint. It is based on a comparison between baseline and endpoint scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by patients in their diaries.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=120 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Number of Participants With a ≥ 2-points Reduction on the Weekly Average of the Daily 24-hour Average Pain Scale at 12 Weeks	59 participants	64 participants	68 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

The LSEQ assesses the effects of psychoactive compounds on sleep and early morning behavior. Participants mark a series of 100 mm line analogue scales, indicating the direction and magnitude of any changes in behavioral state they experience following administration of the drug. Scores are represented in millimeters, higher scores indicate better sleep and better early morning behavior. Subscale score ranges: GTS=0-300, QOS=0-200, AFS=0-200, BFW=0-300. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=124 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=119 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=118 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Leeds Sleep Evaluation Questionnaire (LSEQ) Subscales of Ease of Going to Sleep (GTS), Awakening (AFS), and Behavior Following Wakefulness (BFW), Quality of Sleep (QOS) QOS, n=121, n=118, n=118	9.32 units on a scale Standard Error 4.01	7.39 units on a scale Standard Error 4.24	9.64 units on a scale Standard Error 4.06
Mean Change From Baseline to 12 Weeks in Leeds Sleep Evaluation Questionnaire (LSEQ) Subscales of Ease of Going to Sleep (GTS), Awakening (AFS), and Behavior Following Wakefulness (BFW), Quality of Sleep (QOS) AFS, n=122, n=118, n=118	10.02 units on a scale Standard Error 3.71	8.14 units on a scale Standard Error 3.92	11.86 units on a scale Standard Error 3.73
Mean Change From Baseline to 12 Weeks in Leeds Sleep Evaluation Questionnaire (LSEQ) Subscales of Ease of Going to Sleep (GTS), Awakening (AFS), and Behavior Following Wakefulness (BFW), Quality of Sleep (QOS) GTS, n=122, n=119, n=118	10.96 units on a scale Standard Error 4.83	17.40 units on a scale Standard Error 5.06	14.75 units on a scale Standard Error 4.92
Mean Change From Baseline to 12 Weeks in Leeds Sleep Evaluation Questionnaire (LSEQ) Subscales of Ease of Going to Sleep (GTS), Awakening (AFS), and Behavior Following Wakefulness (BFW), Quality of Sleep (QOS) BFW, n=124, n=115, n=118	19.67 units on a scale Standard Error 5.65	21.04 units on a scale Standard Error 6.03	14.33 units on a scale Standard Error 5.77

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Total scores range from 0 to 30, higher values indicate greater disruption in the patient's life. Item 1 assesses the effect of the patient's symptoms on their work/school schedule, Item 2 on their social life/leisure activities, and Item 3 on their family life/home responsibilities. Subscales scores range: 0-10, higher values indicate greater disruption in the patient's life. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=118 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=124 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=119 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Sheehan Disability Scale (SDS) - Total Score and Scores for Items 1 to 3 Total	-4.96 units on a scale Standard Error 0.66	-3.47 units on a scale Standard Error 0.65	-4.54 units on a scale Standard Error 0.66
Mean Change From Baseline to 12 Weeks in Sheehan Disability Scale (SDS) - Total Score and Scores for Items 1 to 3 Item 1	-1.96 units on a scale Standard Error 0.31	-1.21 units on a scale Standard Error 0.33	-1.95 units on a scale Standard Error 0.32
Mean Change From Baseline to 12 Weeks in Sheehan Disability Scale (SDS) - Total Score and Scores for Items 1 to 3 Item 2	-1.64 units on a scale Standard Error 0.24	-1.12 units on a scale Standard Error 0.23	-1.53 units on a scale Standard Error 0.24
Mean Change From Baseline to 12 Weeks in Sheehan Disability Scale (SDS) - Total Score and Scores for Items 1 to 3 Item 3	-1.70 units on a scale Standard Error 0.22	-1.17 units on a scale Standard Error 0.22	-1.54 units on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All participants who were enrolled in the study.

Outcome measures

Outcome measures
Measure	Pregabalin n=134 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Nausea	0 participants	4 participants	4 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Peripheral Oedema	5 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Insomnia	0 participants	4 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Somnolence	1 participants	2 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Anxiety	0 participants	1 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Dizziness	0 participants	0 participants	2 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Dysuria	0 participants	2 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Hyperhidrosis	0 participants	1 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Sedation	1 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Allergic Oedema	1 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Anorgasmia	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Increased Blood Creatine	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Increased Blood Glucose	1 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Bruxism	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Cerebrovascular Accident	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Chest Discomfort	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Depression	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Dermatitis	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Diarrhoea	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Dry mouth	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Enterovirus Infection	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Fatigue	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Generalized Oedema	1 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Facial Hypoaesthesia	1 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Lacunar Infarction	1 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Loss of Consciousness	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Lymphoma	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Mental Impairment	1 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Muscular Weakness	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Myoclonus	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Pollakiuria	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Pulomnary Embolism	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Rash	0 participants	0 participants	1 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Sleep Disorder	0 participants	1 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Urticaria	1 participants	0 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Headache	0 participants	2 participants	0 participants
Summary of Adverse Events and Serious Adverse Events Leading to Discontinuation Vomiting	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

14-item subject-rated scale assessing medication related changes in sexual activity + functioning. Structured interview/questionnaire. It measures five dimensions of sexual behavior: pleasure; desire/frequency; desire/interest; arousal; and orgasm. The total score is obtained across all 5 dimensions, ranging from 14 to 70. Subscale score ranges: desire/frequency=2-10; desire/interest=3-15; pleasure=1-5; arousal=3-15; orgasm=3-15. Higher scores = better sexual functioning. Least-squares means: adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=101 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=109 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=109 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, total; n=62, n=67, n=66	-0.53 units on a scale Standard Error 0.80	0.48 units on a scale Standard Error 0.77	1.29 units on a scale Standard Error 0.79
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/interest; n=42, n=42, n=45	-0.17 units on a scale Standard Error 0.32	0.34 units on a scale Standard Error 0.33	0.01 units on a scale Standard Error 0.32
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, total; n=39; n=42, n=43	-0.01 units on a scale Standard Error 1.10	1.12 units on a scale Standard Error 1.10	-0.61 units on a scale Standard Error 1.08
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, pleasure; n=64, n=67, n=69	0.08 units on a scale Standard Error 0.12	-0.06 units on a scale Standard Error 0.11	0.13 units on a scale Standard Error 0.11
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, pleasure; n=40, n=42, n=43	0.15 units on a scale Standard Error 0.16	0.47 units on a scale Standard Error 0.16	-0.09 units on a scale Standard Error 0.16
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/frequency; n=65, n=67, n=69	-0.02 units on a scale Standard Error 0.16	0.06 units on a scale Standard Error 0.16	0.16 units on a scale Standard Error 0.16
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/frequency; n=42, n=42, n=43	0.21 units on a scale Standard Error 0.21	0.26 units on a scale Standard Error 0.22	0.30 units on a scale Standard Error 0.21
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/interest; n=65, n=67, n=70	-0.27 units on a scale Standard Error 0.24	-0.19 units on a scale Standard Error 0.24	0.05 units on a scale Standard Error 0.24
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, arousal; n=65, n=67, n=70	0.17 units on a scale Standard Error 0.26	0.52 units on a scale Standard Error 0.26	0.52 units on a scale Standard Error 0.26
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, arousal; n=40, n=42, n=45	-0.11 units on a scale Standard Error 0.34	0.07 units on a scale Standard Error 0.35	-0.30 units on a scale Standard Error 0.33
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, orgasm; n=64, n=67, n=69	-0.39 units on a scale Standard Error 0.27	0.18 units on a scale Standard Error 0.26	0.17 units on a scale Standard Error 0.26
Mean Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, orgasm; n=40, n=42, n=43	0.31 units on a scale Standard Error 0.39	-0.05 units on a scale Standard Error 0.40	-0.85 units on a scale Standard Error 0.39

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) and with baseline values within the normal range were included in the analysis.

14-item subject-rated scale assessing changes in sexual activity and functioning; structured interview/questionnaire, designed to measure medication related changes in sexual functioning. 5 dimensions of sexual behavior: pleasure; desire/frequency; desire/interest; arousal; orgasm. Total score: obtained across all 5 dimensions, ranges from 14 to 70. Subscale scores: desire/frequency=2-10; desire/interest=3-15; pleasure=1-5; arousal=3-15; orgasm=3-15. Higher scores = better sexual functioning. Categories: better=positive change in score; same=no change in score; worse=negative change in score.

Outcome measures

Outcome measures
Measure	Pregabalin n=134 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/frequency, better; n=42, n=42, n=43	11 participants	12 participants	12 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, total, better; n=62, n=67, n=66	24 participants	26 participants	31 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, total, same; n=62, n=67, n=66	9 participants	9 participants	11 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, total, worse; n=62, n=67, n=66	29 participants	32 participants	24 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, total, better; n=39, n=42, n=43	13 participants	23 participants	18 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, total, same; n=39, n=42, n=43	5 participants	5 participants	7 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, total, worse; n=39, n=42, n=43	21 participants	14 participants	18 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, pleasure, better; n=64, n=67, n=69	13 participants	11 participants	21 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, pleasure, same; n=64, n=67, n=69	39 participants	40 participants	32 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, pleasure, worse; n=64, n=67, n=69	12 participants	16 participants	16 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, pleasure, better; n=40, n=42, n=43	10 participants	16 participants	6 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, pleasure, same; n=40, n=42, n=43	23 participants	21 participants	32 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, pleasure, worse; n=40, n=42, n=43	7 participants	5 participants	5 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/frequency, better; n=65, n=67, n=69	12 participants	20 participants	24 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/frequency, same; n=65, n=67, n=69	36 participants	29 participants	23 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/frequency, worse; n=65, n=67, n=69	17 participants	18 participants	22 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/frequency, same; n=42, n=42, n=43	21 participants	21 participants	24 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/interest, same; n=65, n=67, n=70	19 participants	19 participants	17 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/frequency, worse; n=42, n=42, n=43	10 participants	9 participants	7 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/interest, better; n=65, n=67, n=70	20 participants	18 participants	26 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, desire/interest, worse; n=65, n=67, n=70	26 participants	30 participants	27 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/interest, better; n=42, n=42, n=45	13 participants	18 participants	16 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/interest, same; n=42, n=42, n=45	12 participants	14 participants	17 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, desire/interest, worse; n=42, n=42, n=45	17 participants	10 participants	12 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, arousal, better; n=65, n=67, n=70	20 participants	24 participants	23 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, arousal, same; n=65, n=67, n=70	28 participants	29 participants	33 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, arousal, worse; n=65, n=67, n=70	17 participants	14 participants	14 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, arousal, better; n=40, n=42, n=45	11 participants	18 participants	15 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, arousal, same; n=40, n=42, n=45	14 participants	10 participants	16 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, arousal, worse; n=40, n=42, n=45	15 participants	14 participants	14 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, orgasm, better; n=64, n=67, n=69	12 participants	18 participants	17 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, orgasm, same; n=40, n=42, n=43	13 participants	13 participants	16 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, orgasm, same; n=64, n=67, n=69	29 participants	31 participants	29 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores male, orgasm, worse; n=64, n=67, n=69	23 participants	18 participants	23 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, orgasm, better; n=40, n=42, n=43	15 participants	17 participants	11 participants
Categorical Change From Baseline to 12 Weeks in Sexual Functioning Questionnaire (CSFQ) Total Score and Subscale Scores female, orgasm, worse; n=40, n=42, n=43	12 participants	12 participants	16 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

The Portland Neurotoxicity Scale is a 15-item, patient-completed questionnaire designed to assess the degree of impact of anti-epileptic drug therapy on a number of cognitive and somatomotor parameters. The total score ranges from 15-135 with higher scores indicating more toxicity. The cognitive toxicity score ranges from 10-90 and the somatomotor toxicity score ranges from 5-45, for both higher scores indicate more toxicity. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=126 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=129 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=129 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores cognitive toxicity, n=126, n=129, n=128	-5.12 units on a scale Standard Error 1.18	-6.23 units on a scale Standard Error 1.23	-5.29 units on a scale Standard Error 1.16
Mean Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores total, n=122, n=126, n=128	-6.27 units on a scale Standard Error 1.63	-8.92 units on a scale Standard Error 1.70	-7.29 units on a scale Standard Error 1.59
Mean Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores somatomotor toxicity, n=122, n=126, n=129	-1.36 units on a scale Standard Error 0.51	-2.58 units on a scale Standard Error 0.54	-1.91 units on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

The Portland Neurotoxicity Scale is a 15-item, patient-completed questionnaire designed to assess the degree of impact of anti-epileptic drug therapy on a number of cognitive and somatomotor parameters. Categories: better=negative change in score; same=no change in score; worse=positive change in score.

Outcome measures

Outcome measures
Measure	Pregabalin n=126 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=129 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=129 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores worse, total; n=122, n=126, n=128	46 participants	37 participants	38 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores same, somatomotor toxicity; n=122, n=126, n=129	15 participants	19 participants	19 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores better, total; n=122, n=126, n=128	68 participants	84 participants	86 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores same, total; n=122, n=126, n=128	8 participants	5 participants	4 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores better, cognitive toxicity; n=126, n=129, n=128	75 participants	80 participants	82 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores same, cognitive toxicity; n=126, n=129, n=128	9 participants	6 participants	5 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores worse, cognitive toxicity; n=126, n=129, n=128	42 participants	43 participants	41 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores better, somatomotor toxicity; n=122, n=126, n=129	60 participants	74 participants	74 participants
Categorial Change From Baseline to 12 Weeks in Portland Neurotoxicity Scale - Total Score and Subscale Scores worse, somatomotor toxicity; n=122, n=126, n=129	47 participants	33 participants	36 participants

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Contribution to reduction in pain directly by treatment and indirectly by treatment through the reduction of depressive symptoms using path analysis. The direct treatment effect estimates the mean drug difference in pain reduction directly through treatment; the indirect treatment effect estimates the contribution that treatment plays to the mean drug difference in pain reduction indirectly through the reduction in mood symptoms; the total effect estimates the drug difference in reducing pain in sum through the specified path of direct and indirect treatment effects.

Outcome measures

Outcome measures
Measure	Pregabalin n=234 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Path Analysis of Improvement in Pain Through Improvement in Depressive Symptoms Direct Treatment Effect	-0.449 coefficient	—	—
Path Analysis of Improvement in Pain Through Improvement in Depressive Symptoms Indirect Treatment Effect	0.014 coefficient	—	—
Path Analysis of Improvement in Pain Through Improvement in Depressive Symptoms Total Treatment Effect	-0.435 coefficient	—	—

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=121 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=125 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Beck Depression Inventory II (BDI-II) Total Score	-2.57 units on a scale Standard Error 0.58	-3.13 units on a scale Standard Error 0.60	-2.54 units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

The Resource Utilization Scale measures direct and indirect costs (collected only for US sites). Direct costs include inpatient and outpatient costs, while indirect costs include lost days of work and caregiver time spent with patients. Inpatient costs include costs associated with hospitalizations and time spent in emergency rooms and psychiatric rooms. Outpatient costs include costs associated with visits to various health care providers, home health care by health care providers, and partial care.

Outcome measures

Outcome measures
Measure	Pregabalin n=134 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale days of partial care, lower, n=93, n=95, n=90	0 participants	0 participants	1 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale nights of partial care, greater, n=92, n=95, n=91	1 participants	1 participants	2 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale nights of partial care, same, n=92, n=95, n=91	91 participants	94 participants	89 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale nights of partial care, lower, n=92, n=95, n=91	0 participants	0 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale ER visits-psychiatric, greater, n=93, n=94, n=91	0 participants	0 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale ER visits-psychiatric, same, n=93, n=94, n=91	91 participants	94 participants	91 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale ER visits-psychiatric, lower, n=93, n=94, n=91	2 participants	0 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale ER visits-nonpsychiatric, greater,n=91, n=95, n=88	3 participants	4 participants	4 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale ER visits-nonpsychiatric, same,n=91, n=95, n=88	83 participants	85 participants	78 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale unpaid care, greater, n=84, n=87, n=86	2 participants	0 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale ER visits-nonpsychiatric, lower,n=91, n=95, n=88	5 participants	6 participants	6 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale unpaid care, same, n=84, n=87, n=86	82 participants	87 participants	85 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale phone mental health, greater,n=94, n=95, n=90	1 participants	1 participants	2 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale phone mental health, same,n=94, n=95, n=90	92 participants	93 participants	87 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale phone mental health, lower,n=94, n=95, n=90	1 participants	1 participants	1 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale nonpsychiatric visits, greater, n=89, n=94, n=83	24 participants	20 participants	18 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale nonpsychiatric visits, same, n=89, n=94, n=83	44 participants	46 participants	45 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale nonpsychiatric visits, lower, n=89, n=94, n=83	21 participants	28 participants	20 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale unpaid care, lower, n=84, n=87, n=86	0 participants	0 participants	1 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale missed work caregiver, greater, n=6, n=9, n=5	0 participants	0 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale missed work caregiver, same, n=6, n=9, n=5	6 participants	8 participants	5 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale missed work caregiver, lower, n=6, n=9, n=5	0 participants	1 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale paid care, greater, n=60, n=58, n=58	0 participants	0 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale paid care, same, n=60, n=58, n=58	60 participants	58 participants	58 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale paid care, less, n=60, n=58, n=58	0 participants	0 participants	0 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale hours worked, same, n=86, n=90, n=83	65 participants	66 participants	59 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale psychiatric visits, greater, n=92, n=93, n=90	2 participants	0 participants	2 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale psychiatric visits, lower, n=92, n=93, n=90	2 participants	2 participants	4 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale outpatient group visits, greater, n=91, n=92, n=91	0 participants	0 participants	1 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale outpatient ind. visits, same, n=91, n=88, n=90	84 participants	84 participants	81 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale hours worked, greater, n=86, n=90, n=83	10 participants	12 participants	13 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale hours worked, lower, n=86, n=90, n=83	11 participants	12 participants	11 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale hours volunteered, greater, n=86, n=91, n=82	7 participants	8 participants	10 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale hours volunteered, same, n=86, n=91, n=82	66 participants	77 participants	66 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale hours volunteered, lower, n=86, n=91, n=82	13 participants	6 participants	6 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale psychiatric visits, same, n=92, n=93, n=90	88 participants	91 participants	84 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale outpatient group visits, same, n=91, n=92, n=91	90 participants	92 participants	89 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale outpatient group visits, lower, n=91, n=92, n=91	1 participants	0 participants	1 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale outpatient ind. visits, greater, n=91, n=88, n=90	3 participants	1 participants	4 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale outpatient ind. visits, lower, n=91, n=88, n=90	4 participants	3 participants	5 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale days of partial care, greater, n=93, n=95, n=90	2 participants	1 participants	2 participants
Categorical Change From Baseline to 12 Weeks in Number of Patients Using Health Care as Measured by the Resource Utilization Scale days of partial care, same, n=93, n=95, n=90	91 participants	94 participants	87 participants

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Number of participants who discontinued. The reasons for discontinuation are presented in the participant flow.

Outcome measures

Outcome measures
Measure	Pregabalin n=134 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Summary of Number of Participants Who Discontinued	38 participants	51 participants	36 participants

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is the number of days required to first achieve a nominal outcome reflecting whether or not a clinically-important efficacy outcome was achieved. It is based on a comparison between baseline and post-baseline scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by patients in their diaries.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=120 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Time to First ≥ 30% Reduction in Weekly Mean 24 Hour Average Pain Score	35.0 days Interval 28.0 to 55.0	28.0 days Interval 20.0 to 35.0	28.0 days Interval 21.0 to 35.0

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is the number of days to first achieve ≥50% reduction, baseline to endpoint, in the weekly means of the 24-hour average pain severity via daily patient assessments using an ordinal scale (scores from 0 (no pain) to 10 (worst possible pain). The median time to first ≥50% reduction with some measure of dispersion could not be calculated for each treatment group. The number of patients who reached a ≥50% reduction in weekly mean 24 hour average pain score are presented in outcome measure 20.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is the number of days to first achieve an outcome using the weekly means of the 24-hour average pain severity via daily patient assessments using an ordinal scale (scores from 0 (no pain) to 10 (worst possible pain). Sustained response: ≥30% reduction, baseline to endpoint, with 30% reduction from baseline ≥2 weeks prior to endpoint, remaining at ≥20% reduction between. The median time to sustained response with some measure of dispersion could not be calculated for each treatment group.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is the number of days required to first achieve a nominal outcome reflecting whether or not a clinically-important efficacy outcome was achieved. It is based on a comparison between baseline and post-baseline scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by patients in their diaries.

Outcome measures

Outcome measures
Measure	Pregabalin n=127 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=120 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=125 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Time to First ≥ 2 Points Reduction in Weekly Mean 24 Hour Average Pain Score	56.0 days Interval 39.0 to 80.0	35.0 days Interval 28.0 to 53.0	28.0 days Interval 22.0 to 42.0

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Data presented represent the weekly mean of the scores of the average pain severity over the last 24 hours. Scores are based on daily assessments recorded by patients in their diaries. It was planned to analyze participants stratified by the presence or absence of a co-morbidity with GAD. However, due to the low number of participants with GAD in the study this analysis was not possible.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: The per-protocol sub-population of all randomized participants with a baseline value and \>= 1 non-missing post-baseline value (modified intent-to-treat population) was included in the analysis.

Ordinal scale: 0=no pain, 10=worst possible pain. Data=weekly mean of scores of average pain severity over last 24 hours (h). Scores: daily assessments recorded by patients in diaries. Only patients adhering to key protocol criteria included: baseline Weekly Mean 24h Average Pain Score ≥4; 80-120% compliant with study Drug, each visit; baseline Michigan Neuropathy Screening Instrument Physical Assessment Total Score ≥3; gabapentin taper ≤14 days, no HbA1c ≥12% post randomization; no contraindicated medications used. Least-squares means=adjustment due to baseline severity + investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=94 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=77 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=103 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Weekly Mean Change From Baseline to 12 Weeks in 24 Hour Average Pain Severity - Only Participants Who Adhered to Key Protocol Requirements (Per-Protocol Population) change	-2.12 units on a scale Standard Error 0.23	-2.58 units on a scale Standard Error 0.27	-2.40 units on a scale Standard Error 0.23
Weekly Mean Change From Baseline to 12 Weeks in 24 Hour Average Pain Severity - Only Participants Who Adhered to Key Protocol Requirements (Per-Protocol Population) baseline	5.74 units on a scale Standard Error 1.30	6.02 units on a scale Standard Error 1.60	5.74 units on a scale Standard Error 1.42

SECONDARY outcome

Timeframe: baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks

Population: Analyzed were all participants with a baseline and at least 1 non-missing post-baseline value. Last observation carried forward analysis.

This is an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Data presented represent the weekly mean of the scores of the average pain severity over the last 24 hours. Scores are based on daily assessments recorded by patients in their diaries. De novo: use of gabapentin for \<56 contiguous days prior to randomization. Prior use: use of gabapentin for \>=56 contiguous days prior to randomization. Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=134 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 4	-0.84 units on a scale Standard Error 0.32	-2.35 units on a scale Standard Error 0.35	-1.67 units on a scale Standard Error 0.32
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 8	-1.26 units on a scale Standard Error 0.35	-2.78 units on a scale Standard Error 0.39	-2.06 units on a scale Standard Error 0.35
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 11	-1.48 units on a scale Standard Error 0.35	-2.98 units on a scale Standard Error 0.39	-2.09 units on a scale Standard Error 0.35
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 12	-1.62 units on a scale Standard Error 0.36	-3.08 units on a scale Standard Error 0.40	-2.10 units on a scale Standard Error 0.36
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 2	-0.70 units on a scale Standard Error 0.19	-0.99 units on a scale Standard Error 0.19	-1.28 units on a scale Standard Error 0.19
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 6	-1.92 units on a scale Standard Error 0.23	-2.03 units on a scale Standard Error 0.23	-1.98 units on a scale Standard Error 0.23
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 7	-1.93 units on a scale Standard Error 0.23	-2.14 units on a scale Standard Error 0.23	-2.17 units on a scale Standard Error 0.23
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 5	-1.72 units on a scale Standard Error 0.22	-1.95 units on a scale Standard Error 0.23	-1.96 units on a scale Standard Error 0.22
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, baseline	5.24 units on a scale Standard Error 1.07	5.39 units on a scale Standard Error 1.48	5.49 units on a scale Standard Error 1.45
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 1	-0.22 units on a scale Standard Error 0.24	-0.71 units on a scale Standard Error 0.27	-0.38 units on a scale Standard Error 0.25
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 2	-0.39 units on a scale Standard Error 0.27	-1.22 units on a scale Standard Error 0.31	-1.10 units on a scale Standard Error 0.28
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 3	-0.71 units on a scale Standard Error 0.30	-1.83 units on a scale Standard Error 0.30	-1.62 units on a scale Standard Error 0.30
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 5	-0.95 units on a scale Standard Error 0.33	-2.65 units on a scale Standard Error 0.37	-1.81 units on a scale Standard Error 0.33
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 6	-1.09 units on a scale Standard Error 0.34	-2.64 units on a scale Standard Error 0.38	-1.88 units on a scale Standard Error 0.34
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 7	-1.08 units on a scale Standard Error 0.34	-2.73 units on a scale Standard Error 0.38	-2.07 units on a scale Standard Error 0.34
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 9	-1.21 units on a scale Standard Error 0.34	-2.89 units on a scale Standard Error 0.38	-2.10 units on a scale Standard Error 0.35
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) de novo, week 10	-1.42 units on a scale Standard Error 0.35	-2.86 units on a scale Standard Error 0.39	-1.92 units on a scale Standard Error 0.35
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, baseline	5.91 units on a scale Standard Error 1.55	5.99 units on a scale Standard Error 1.52	5.92 units on a scale Standard Error 1.48
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 1	-0.30 units on a scale Standard Error 0.17	-0.48 units on a scale Standard Error 0.16	-0.65 units on a scale Standard Error 0.17
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 3	-1.18 units on a scale Standard Error 0.20	-1.32 units on a scale Standard Error 0.20	-1.68 units on a scale Standard Error 0.21
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 4	-1.64 units on a scale Standard Error 0.21	-1.61 units on a scale Standard Error 0.22	-1.75 units on a scale Standard Error 0.22
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 8	-1.89 units on a scale Standard Error 0.23	-2.16 units on a scale Standard Error 0.24	-2.31 units on a scale Standard Error 0.23
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 9	-2.04 units on a scale Standard Error 0.23	-2.38 units on a scale Standard Error 0.24	-2.37 units on a scale Standard Error 0.23
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 10	-2.14 units on a scale Standard Error 0.23	-2.45 units on a scale Standard Error 0.24	-2.44 units on a scale Standard Error 0.24
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 11	-2.27 units on a scale Standard Error 0.23	-2.46 units on a scale Standard Error 0.24	-2.41 units on a scale Standard Error 0.24
Weekly Mean Change in 24 Hour Average Pain Severity by Week by Gabapentin Exposure Subgroup (de Novo Versus Prior Use) prior use, week 12	-2.39 units on a scale Standard Error 0.23	-2.46 units on a scale Standard Error 0.24	-2.53 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized patients.

Presented are numbers of participants who discontinued due to a change from baseline in laboratory analytes or vital signs.

Outcome measures

Outcome measures
Measure	Pregabalin n=134 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Discontinuations for Abnormal Laboratory Analytes, Vital Signs, Overall and for Each Measure Increased blood creatinine	0 participants	0 participants	1 participants
Discontinuations for Abnormal Laboratory Analytes, Vital Signs, Overall and for Each Measure Increased blood glucose	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=130 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=133 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=132 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Blood Pressure Diastolic	0.18 millimeter mercury Standard Error 0.92	2.24 millimeter mercury Standard Error 0.97	-0.79 millimeter mercury Standard Error 0.91
Mean Change From Baseline to 12 Weeks in Blood Pressure Systolic	-3.31 millimeter mercury Standard Error 1.44	-3.08 millimeter mercury Standard Error 1.54	-2.08 millimeter mercury Standard Error 1.43

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=130 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=133 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=132 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Heart Rate	-1.30 beats per minute Standard Error 0.97	0.80 beats per minute Standard Error 1.02	1.05 beats per minute Standard Error 0.96

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Least-squares means represent adjustment due to baseline severity and investigative site.

Outcome measures

Outcome measures
Measure	Pregabalin n=130 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=132 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=132 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Body Weight	1.00 kilogram Standard Error 0.36	-2.39 kilogram Standard Error 0.38	-1.06 kilogram Standard Error 0.36

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) and with baseline values within the normal range were included in the analysis.

Elevated systolic blood pressure: \>=130 millimeter mercury (mm Hg) + an increase of \>=10 mm Hg if baseline \<130 mm Hg. Elevated diastolic blood pressure: \>=85 mm Hg + an increase of \>=10 mm Hg if baseline \<85 mm Hg.

Outcome measures

Outcome measures
Measure	Pregabalin n=94 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=98 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=100 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Number of Participants With Treatment-emergent Elevated Blood Pressure diastolic, n=94, n=98, n=100	11 participants	12 participants	13 participants
Number of Participants With Treatment-emergent Elevated Blood Pressure systolic, n=42, n=39, n=56	20 participants	15 participants	16 participants

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) and with baseline values within the normal range were included in the analysis.

Elevated heart rate: \>=100 beats per minute (bpm) + an increase of \>=10 bpm if baseline \<100 bpm.

Outcome measures

Outcome measures
Measure	Pregabalin n=126 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=128 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=127 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Number of Participants With Treatment-Emergent Elevated Heart Rate	2 participants	9 participants	6 participants

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Treatment-emergent high body weight: weight at last visit \>=107% of baseline weight. Treatment-emergent low body weight: weight at last visit \<=93% of baseline weight.

Outcome measures

Outcome measures
Measure	Pregabalin n=130 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=132 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=132 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Number of Participants With Treatment-Emergent Changes in Body Weight high	6 participants	1 participants	3 participants
Number of Participants With Treatment-Emergent Changes in Body Weight low	2 participants	10 participants	8 participants

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Aspartate aminotransferase = AST Alanine aminotransferase = ALT Gamma glutamyl transferase = GGT Alkaline phosphatase = AlkPhos

Outcome measures

Outcome measures
Measure	Pregabalin n=121 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=123 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=120 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels baseline, ALT, n=120, n=122, n=120	23.88 units/liter Standard Deviation 10.14	25.04 units/liter Standard Deviation 13.18	24.39 units/liter Standard Deviation 10.79
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels baseline, AST, n=119, n=121, n=118	22.55 units/liter Standard Deviation 7.64	22.84 units/liter Standard Deviation 8.70	23.42 units/liter Standard Deviation 8.19
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels change, AST, n=119, n=121, n=118	1.12 units/liter Standard Deviation 7.62	-0.52 units/liter Standard Deviation 6.82	-0.48 units/liter Standard Deviation 7.71
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels change, ALT, n=120, n=122, n=120	-0.13 units/liter Standard Deviation 7.86	-0.16 units/liter Standard Deviation 10.45	0.03 units/liter Standard Deviation 9.53
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels baseline, GGT, n=121, n=123, n=120	40.80 units/liter Standard Deviation 53.08	34.29 units/liter Standard Deviation 25.53	43.93 units/liter Standard Deviation 48.45
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels change, GGT, n=121, n=123, n=120	1.17 units/liter Standard Deviation 39.35	-3.03 units/liter Standard Deviation 15.56	-2.55 units/liter Standard Deviation 22.85
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels baseline, AlkPhos, n=121, n=123, n=120	84.97 units/liter Standard Deviation 29.36	83.74 units/liter Standard Deviation 38.27	82.18 units/liter Standard Deviation 28.39
Mean Change From Baseline to 12 Weeks in Hepatic Enzyme Serum Levels change, AlkPhos, n=121, n=123, n=120	2.80 units/liter Standard Deviation 40.32	0.55 units/liter Standard Deviation 18.21	1.78 units/liter Standard Deviation 12.84

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Outcome measures

Outcome measures
Measure	Pregabalin n=120 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=123 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=120 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Total Bilirubin baseline	8.43 micromole/liter Standard Deviation 4.50	8.07 micromole/liter Standard Deviation 3.99	8.23 micromole/liter Standard Deviation 5.07
Mean Change From Baseline to 12 Weeks in Total Bilirubin change	-0.51 micromole/liter Standard Deviation 3.48	-0.28 micromole/liter Standard Deviation 2.60	-0.42 micromole/liter Standard Deviation 3.39

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Outcome measures

Outcome measures
Measure	Pregabalin n=86 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=82 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=78 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Fasting Plasma Glucose baseline	8.24 millimole/liter Standard Deviation 3.31	8.45 millimole/liter Standard Deviation 3.65	7.99 millimole/liter Standard Deviation 3.82
Mean Change From Baseline to 12 Weeks in Fasting Plasma Glucose change	0.16 millimole/liter Standard Deviation 3.97	0.19 millimole/liter Standard Deviation 2.86	0.67 millimole/liter Standard Deviation 2.75

SECONDARY outcome

Timeframe: baseline, 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) were included in the analysis.

Outcome measures

Outcome measures
Measure	Pregabalin n=117 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=124 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=119 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Mean Change From Baseline to 12 Weeks in Hemoglobin A1C baseline	7.57 percent Standard Deviation 1.61	7.51 percent Standard Deviation 1.44	7.16 percent Standard Deviation 1.44
Mean Change From Baseline to 12 Weeks in Hemoglobin A1C change	-0.12 percent Standard Deviation 1.00	-0.01 percent Standard Deviation 0.71	0.07 percent Standard Deviation 0.80

SECONDARY outcome

Timeframe: baseline through 12 weeks

Population: All randomized participants with a baseline value and at least 1 non-missing post-baseline value (modified intent-to-treat population) and with baseline values within the normal range were included in the analysis.

Treatment-emergent: within range at baseline, out of range after baseline. Ranges in Units/Liter (U/L). Aspartate Aminotransferase (AST): female (f): \>34, male (m): \>36. Alanine Aminotransferase (ALT): f:\<69 years (yr) \>34, ≥69yr \>32; m: \<69yr \>43, ≥69yr \>35. Total Bilirubin (TBili): \>21. Gamma Glutamyl Transferase (GGT): f: \<59yr \>49, ≥59yr \>50; m: \<59yr \>61, ≥59yr \>50. Fasting Plasma Glucose (FPG): \<59yr \>6.4, ≥59yr \>6.7. Hemoglobin A1C (HbA1C) \>6%. Alkaline Phosphatase (AlkPhos): f: 18-50yr \>106, 50-70yr \>123, 70-80yr \>164, ≥80yr \>221; m: 18-50yr \>129, 50-70yr \>131, 70-80yr \>156, ≥80yr \>187

Outcome measures

Outcome measures
Measure	Pregabalin n=121 Participants Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=124 Participants Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=120 Participants Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Number of Patients With Treatment-Emergent Elevated Laboratory Analytes AST, n=113, n=116, n=109	4 participants	6 participants	4 participants
Number of Patients With Treatment-Emergent Elevated Laboratory Analytes ALT, n=111, n=104, n=110	3 participants	6 participants	10 participants
Number of Patients With Treatment-Emergent Elevated Laboratory Analytes TBili, n=119, n=121, n=116	2 participants	0 participants	0 participants
Number of Patients With Treatment-Emergent Elevated Laboratory Analytes GGT, n=102, n=105, n=96	2 participants	6 participants	6 participants
Number of Patients With Treatment-Emergent Elevated Laboratory Analytes FPG, n=33, n=30, n=36	7 participants	11 participants	18 participants
Number of Patients With Treatment-Emergent Elevated Laboratory Analytes HbA1C, n=17, n=18, n=29	6 participants	2 participants	10 participants
Number of Patients With Treatment-Emergent Elevated Laboratory Analytes AlkPhos, n=112, n=114, n=113	4 participants	3 participants	4 participants

Adverse Events

Pregabalin

Serious events: 6 serious events

Other events: 87 other events

Deaths: 0 deaths

Duloxetine

Serious events: 3 serious events

Other events: 100 other events

Deaths: 0 deaths

Gabapentin + Duloxetine

Serious events: 5 serious events

Other events: 88 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pregabalin n=134 participants at risk Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 participants at risk Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 participants at risk Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Cardiac disorders Atrial fibrillation	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Cardiac disorders Cardiac failure congestive	0.75% 1/134 • Number of events 1	0.00% 0/138	0.74% 1/135 • Number of events 1
Cardiac disorders Cor pulmonale	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
Gastrointestinal disorders Diverticulum intestinal	0.00% 0/134	0.00% 0/138	0.74% 1/135 • Number of events 1
Gastrointestinal disorders Dysphagia	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
General disorders Chest pain	0.75% 1/134 • Number of events 1	0.00% 0/138	0.74% 1/135 • Number of events 1
Infections and infestations Infection	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
Infections and infestations Osteomyelitis chronic	0.00% 0/134	0.00% 0/138	0.74% 1/135 • Number of events 1
Infections and infestations Pharyngitis	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
Infections and infestations Pneumonia	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/134	0.00% 0/138	0.74% 1/135 • Number of events 1
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Metabolism and nutrition disorders Fluid retention	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
Nervous system disorders Ataxia	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Nervous system disorders Cerebrovascular accident	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Nervous system disorders Dizziness	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Nervous system disorders Lacunar infarction	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
Nervous system disorders Somnolence	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Psychiatric disorders Confusional state	0.00% 0/134	0.72% 1/138 • Number of events 1	0.00% 0/135
Respiratory, thoracic and mediastinal disorders Hypoxia	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	0.75% 1/134 • Number of events 1	0.00% 0/138	0.00% 0/135
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/134	0.00% 0/138	0.74% 1/135 • Number of events 1

Other adverse events

Other adverse events
Measure	Pregabalin n=134 participants at risk Pregabalin (PGB) 50 milligram (mg) three times a day (TID) (US \& Germany) or 75 mg twice daily (BID) (Canada), orally (PO) for 2 weeks, then PGB 100 mg TID (US \& Germany) or 150 mg BID (Canada), PO for 10 weeks.	Duloxetine n=138 participants at risk Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then DLX 60 mg QD, PO for 11 weeks.	Gabapentin + Duloxetine n=135 participants at risk Stable Gabapentin (GAB) + Duloxetine (DLX) 30 milligram (mg) once daily (QD), orally (PO) for 1 week, then stable GAB + DLX 60 mg QD, PO for 11 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 2/134 • Number of events 2	2.9% 4/138 • Number of events 4	1.5% 2/135 • Number of events 3
Musculoskeletal and connective tissue disorders Back pain	2.2% 3/134 • Number of events 3	0.72% 1/138 • Number of events 1	0.74% 1/135 • Number of events 1
Ear and labyrinth disorders Tinnitus	0.00% 0/134	0.72% 1/138 • Number of events 1	3.0% 4/135 • Number of events 4
Eye disorders Vision blurred	3.0% 4/134 • Number of events 4	1.4% 2/138 • Number of events 2	0.74% 1/135 • Number of events 1
Gastrointestinal disorders Constipation	3.0% 4/134 • Number of events 4	2.9% 4/138 • Number of events 5	6.7% 9/135 • Number of events 9
Gastrointestinal disorders Diarrhoea	1.5% 2/134 • Number of events 2	3.6% 5/138 • Number of events 5	3.7% 5/135 • Number of events 6
Gastrointestinal disorders Dry mouth	4.5% 6/134 • Number of events 6	4.3% 6/138 • Number of events 6	3.7% 5/135 • Number of events 5
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/134	2.2% 3/138 • Number of events 3	0.00% 0/135
Gastrointestinal disorders Nausea	1.5% 2/134 • Number of events 3	13.8% 19/138 • Number of events 19	13.3% 18/135 • Number of events 18
Gastrointestinal disorders Vomiting	0.00% 0/134	3.6% 5/138 • Number of events 6	4.4% 6/135 • Number of events 11
General disorders Asthenia	0.00% 0/134	2.9% 4/138 • Number of events 4	0.74% 1/135 • Number of events 1
General disorders Fatigue	5.2% 7/134 • Number of events 7	11.6% 16/138 • Number of events 16	11.1% 15/135 • Number of events 17
General disorders Oedema peripheral	13.4% 18/134 • Number of events 19	1.4% 2/138 • Number of events 3	0.00% 0/135
Infections and infestations Upper respiratory tract infection	3.0% 4/134 • Number of events 4	2.9% 4/138 • Number of events 5	4.4% 6/135 • Number of events 6
Infections and infestations Urinary tract infection	2.2% 3/134 • Number of events 3	0.00% 0/138	0.00% 0/135
Injury, poisoning and procedural complications Muscle strain	0.00% 0/134	2.2% 3/138 • Number of events 3	0.00% 0/135
Investigations Weight decreased	0.00% 0/134	2.2% 3/138 • Number of events 3	0.74% 1/135 • Number of events 1
Investigations Weight increased	3.0% 4/134 • Number of events 5	0.00% 0/138	0.00% 0/135
Metabolism and nutrition disorders Anorexia	0.00% 0/134	2.2% 3/138 • Number of events 3	0.74% 1/135 • Number of events 1
Metabolism and nutrition disorders Decreased appetite	0.00% 0/134	6.5% 9/138 • Number of events 9	4.4% 6/135 • Number of events 6
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/134	2.9% 4/138 • Number of events 4	1.5% 2/135 • Number of events 2
Metabolism and nutrition disorders Obesity	0.00% 0/134	2.2% 3/138 • Number of events 3	1.5% 2/135 • Number of events 2
Musculoskeletal and connective tissue disorders Pain in extremity	2.2% 3/134 • Number of events 4	2.2% 3/138 • Number of events 3	0.00% 0/135
Nervous system disorders Balance disorder	2.2% 3/134 • Number of events 3	0.00% 0/138	0.00% 0/135
Nervous system disorders Diabetic neuropathy	3.7% 5/134 • Number of events 5	2.9% 4/138 • Number of events 4	2.2% 3/135 • Number of events 3
Nervous system disorders Dizziness	4.5% 6/134 • Number of events 6	6.5% 9/138 • Number of events 9	8.9% 12/135 • Number of events 12
Nervous system disorders Headache	2.2% 3/134 • Number of events 3	8.0% 11/138 • Number of events 11	5.2% 7/135 • Number of events 8
Nervous system disorders Hypoaesthesia	1.5% 2/134 • Number of events 2	2.9% 4/138 • Number of events 5	1.5% 2/135 • Number of events 2
Nervous system disorders Somnolence	6.7% 9/134 • Number of events 9	5.8% 8/138 • Number of events 8	3.7% 5/135 • Number of events 5
Nervous system disorders Syncope	0.00% 0/134	0.72% 1/138 • Number of events 1	2.2% 3/135 • Number of events 3
Nervous system disorders Tremor	0.75% 1/134 • Number of events 1	3.6% 5/138 • Number of events 5	0.74% 1/135 • Number of events 1
Psychiatric disorders Anxiety	0.75% 1/134 • Number of events 1	2.2% 3/138 • Number of events 3	0.74% 1/135 • Number of events 1
Psychiatric disorders Depression	1.5% 2/134 • Number of events 2	2.2% 3/138 • Number of events 3	0.00% 0/135
Psychiatric disorders Insomnia	1.5% 2/134 • Number of events 2	12.3% 17/138 • Number of events 17	3.7% 5/135 • Number of events 5
Psychiatric disorders Sleep disorder	1.5% 2/134 • Number of events 2	2.9% 4/138 • Number of events 4	1.5% 2/135 • Number of events 2
Renal and urinary disorders Dysuria	0.00% 0/134	2.2% 3/138 • Number of events 3	2.2% 3/135 • Number of events 3
Renal and urinary disorders Pollakiuria	0.00% 0/134	0.72% 1/138 • Number of events 1	2.2% 3/135 • Number of events 3
Reproductive system and breast disorders Erectile dysfunction	2.2% 3/134 • Number of events 3	2.2% 3/138 • Number of events 3	2.2% 3/135 • Number of events 3
Respiratory, thoracic and mediastinal disorders Cough	0.75% 1/134 • Number of events 1	1.4% 2/138 • Number of events 2	3.0% 4/135 • Number of events 4
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/134	8.0% 11/138 • Number of events 11	4.4% 6/135 • Number of events 6
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/134	0.72% 1/138 • Number of events 3	3.7% 5/135 • Number of events 5
Vascular disorders Hypertension	2.2% 3/134 • Number of events 3	5.1% 7/138 • Number of events 8	2.2% 3/135 • Number of events 3

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60