Trial Outcomes & Findings for Study Of Pregabalin (Lyrica) In Patients With Painful Diabetic Peripheral Neuropathy (NCT NCT01057693)

Last Updated: 2021-01-20

Results Overview

Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. SB baseline refers to the last 7 pain diary entries up to and including Day 1.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

633 participants

Primary outcome timeframe

SB Baseline, Week 19 (DB Phase)

Results posted on

2021-01-20

Participant Flow

Participant milestones

Participant milestones
Measure	Pregabalin SB Participants who were inadequately controlled on their current diabetic peripheral neuropathy (DPN) treatment were switched to single-blind (SB) pregabalin capsules at a starting dose of 150 milligram per day (mg/day) and increased to 300 mg/day, administered three times daily up to Week 6. Participants who experienced greater than or equal to (\>=) 30 percent (%) pain reduction from baseline to Week 6 were eligible for double-blind (DB) treatment phase.	Pregabalin DB Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Single-Blind Phase (Up to Week 6) STARTED	665	0	0
Single-Blind Phase (Up to Week 6) COMPLETED	566	0	0
Single-Blind Phase (Up to Week 6) NOT COMPLETED	99	0	0
Between Single-Blind and Double-Blind STARTED	566	0	0
Between Single-Blind and Double-Blind COMPLETED	296	0	0
Between Single-Blind and Double-Blind NOT COMPLETED	270	0	0
Double-Blind Phase (Week 7 to Week 19) STARTED	0	147	149
Double-Blind Phase (Week 7 to Week 19) Treated	0	147	147
Double-Blind Phase (Week 7 to Week 19) COMPLETED	0	125	113
Double-Blind Phase (Week 7 to Week 19) NOT COMPLETED	0	22	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin SB Participants who were inadequately controlled on their current diabetic peripheral neuropathy (DPN) treatment were switched to single-blind (SB) pregabalin capsules at a starting dose of 150 milligram per day (mg/day) and increased to 300 mg/day, administered three times daily up to Week 6. Participants who experienced greater than or equal to (\>=) 30 percent (%) pain reduction from baseline to Week 6 were eligible for double-blind (DB) treatment phase.	Pregabalin DB Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Single-Blind Phase (Up to Week 6) Adverse Event	45	0	0
Single-Blind Phase (Up to Week 6) Lack of Efficacy	7	0	0
Single-Blind Phase (Up to Week 6) Lost to Follow-up	14	0	0
Single-Blind Phase (Up to Week 6) Protocol Violation	9	0	0
Single-Blind Phase (Up to Week 6) Withdrawal by Subject	22	0	0
Single-Blind Phase (Up to Week 6) Other	2	0	0
Between Single-Blind and Double-Blind Adverse Event	5	0	0
Between Single-Blind and Double-Blind Lack of Efficacy	247	0	0
Between Single-Blind and Double-Blind Lost to Follow-up	1	0	0
Between Single-Blind and Double-Blind Protocol Violation	7	0	0
Between Single-Blind and Double-Blind Withdrawal by Subject	4	0	0
Between Single-Blind and Double-Blind Other	6	0	0
Double-Blind Phase (Week 7 to Week 19) Adverse Event	0	8	11
Double-Blind Phase (Week 7 to Week 19) Lack of Efficacy	0	3	8
Double-Blind Phase (Week 7 to Week 19) Lost to Follow-up	0	2	5
Double-Blind Phase (Week 7 to Week 19) Protocol Violation	0	0	4
Double-Blind Phase (Week 7 to Week 19) Withdrawal by Subject	0	8	6
Double-Blind Phase (Week 7 to Week 19) Other	0	1	0
Double-Blind Phase (Week 7 to Week 19) Randomized, Not Treated	0	0	2

Baseline Characteristics

Study Of Pregabalin (Lyrica) In Patients With Painful Diabetic Peripheral Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin SB n=665 Participants Participants who were inadequately controlled on their current DPN treatment were switched to SB pregabalin capsules at a starting dose of 150 mg/day and increased to 300 mg/day, administered three times daily up to Week 6. Participants who experienced \>=30% pain reduction from baseline to Week 6 were eligible for DB treatment phase.
Age, Customized 18 to 44 Years	58 participants n=5 Participants
Age, Customized 45 to 64 Years	417 participants n=5 Participants
Age, Customized >=65 Years	190 participants n=5 Participants
Sex: Female, Male Female	302 Participants n=5 Participants
Sex: Female, Male Male	363 Participants n=5 Participants

PRIMARY outcome

Timeframe: SB Baseline, Week 19 (DB Phase)

Population: Full analysis set (FAS) included all participants randomized to double-blind treatment who received at least 1 dose of double-blind study treatment. Missing data were imputed using Last Observation Carried Forward (LOCF).

Outcome measures

Outcome measures
Measure	Pregabalin DB n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Change From Single-Blind Baseline in Mean Pain Score at Week 19 During Double-Blind Phase Single-Blind Baseline	6.8 units on a scale Standard Deviation 1.24	6.7 units on a scale Standard Deviation 1.32
Change From Single-Blind Baseline in Mean Pain Score at Week 19 During Double-Blind Phase Change at Week 19 (DB Phase)	-3.9 units on a scale Standard Deviation 1.92	-3.5 units on a scale Standard Deviation 2.10

SECONDARY outcome

Timeframe: SB Baseline up to Week 19

Population: FAS included all participants randomized to double-blind treatment who received at least 1 dose of double-blind study treatment.

Time to loss of pain response (based on the daily pain diary data) during the DB treatment phase was analyzed using survival analysis technique. Loss of pain response was defined as less than (\<) 15% pain response relative to the SB baseline. SB baseline refers to the last 7 pain diary entries up to and including Day 1.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Time to Loss of Pain Response (Double-Blind Phase)	NA days Median and 95% confidence interval (CI) were not estimable because less than 50% participants experienced loss of pain response.	NA days Median and 95% confidence interval (CI) were not estimable because less than 50% participants experienced loss of pain response.

SECONDARY outcome

Timeframe: SB Baseline, Week 6 (SB Phase)

Population: Single-Blind Analysis Set (SBAS) included all participants who were enrolled in single-blind treatment phase and received at least 1 dose of study treatment. "N" (number of participants analyzed): participants who were evaluable for this measure and "n": participants who were evaluable for specified time-point. Missing data were imputed using LOCF.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=663 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Change From Single-Blind Baseline in Mean Pain Score at Week 6 During Single-Blind Phase SB Baseline (n= 663)	6.7 units on a scale Standard Deviation 1.27	—
Change From Single-Blind Baseline in Mean Pain Score at Week 6 During Single-Blind Phase Change at Week 6 (SB Phase) (n= 658)	-2.2 units on a scale Standard Deviation 2.03	—

SECONDARY outcome

Timeframe: Week 1, 2, 3, 4, 5, 6

Population: SBAS included all participants who were enrolled in single-blind treatment phase and received at least one dose of study treatment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for specified time-point.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=657 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Weekly Mean Pain Scores (Single-Blind Phase) Week 1 (n= 657)	6.0 units on a scale Standard Deviation 1.62	—
Weekly Mean Pain Scores (Single-Blind Phase) Week 2 (n= 636)	5.4 units on a scale Standard Deviation 1.82	—
Weekly Mean Pain Scores (Single-Blind Phase) Week 3 (n= 613)	4.9 units on a scale Standard Deviation 1.93	—
Weekly Mean Pain Scores (Single-Blind Phase) Week 4 (n= 585)	4.6 units on a scale Standard Deviation 1.93	—
Weekly Mean Pain Scores (Single-Blind Phase) Week 5 (n= 565)	4.5 units on a scale Standard Deviation 1.92	—
Weekly Mean Pain Scores (Single-Blind Phase) Week 6 (n= 548)	4.3 units on a scale Standard Deviation 2.02	—

SECONDARY outcome

Timeframe: DB Baseline, Week 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19

Population: FAS included all participants randomized to double-blind treatment who received at least 1 dose of double-blind study treatment. Here "n" signifies participants who were evaluable for specified time-point for each arm group, respectively.

Weekly mean pain score was defined as the mean of the daily diary pain ratings split into 7 day intervals. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. SB baseline refers to the last 7 pain diary entries up to and including Day 1. DB baseline refers to the last 7 pain diary entries up to and including DB Day 1.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Weekly Mean Pain Scores (Double-Blind Phase) DB Baseline (n= 147, 147)	3.1 units on a scale Standard Deviation 1.42	3.0 units on a scale Standard Deviation 1.40
Weekly Mean Pain Scores (Double-Blind Phase) Week 7 (n= 144, 145)	3.2 units on a scale Standard Deviation 1.60	3.3 units on a scale Standard Deviation 1.80
Weekly Mean Pain Scores (Double-Blind Phase) Week 9 (n= 140, 133)	3.0 units on a scale Standard Deviation 1.65	3.4 units on a scale Standard Deviation 1.76
Weekly Mean Pain Scores (Double-Blind Phase) Week 10 (n= 138, 133)	3.0 units on a scale Standard Deviation 1.70	3.4 units on a scale Standard Deviation 1.77
Weekly Mean Pain Scores (Double-Blind Phase) Week 17 (n= 128, 115)	2.7 units on a scale Standard Deviation 1.61	2.9 units on a scale Standard Deviation 1.70
Weekly Mean Pain Scores (Double-Blind Phase) Week 19 (n= 115, 104)	2.7 units on a scale Standard Deviation 1.57	2.8 units on a scale Standard Deviation 1.71
Weekly Mean Pain Scores (Double-Blind Phase) Week 8 (n= 143, 142)	3.2 units on a scale Standard Deviation 1.72	3.6 units on a scale Standard Deviation 1.79
Weekly Mean Pain Scores (Double-Blind Phase) Week 11 (n= 138, 128)	2.9 units on a scale Standard Deviation 1.64	3.3 units on a scale Standard Deviation 1.63
Weekly Mean Pain Scores (Double-Blind Phase) Week 12 (n= 135, 123)	2.9 units on a scale Standard Deviation 1.68	3.2 units on a scale Standard Deviation 1.70
Weekly Mean Pain Scores (Double-Blind Phase) Week 13 (n= 134, 122)	2.9 units on a scale Standard Deviation 1.68	3.1 units on a scale Standard Deviation 1.69
Weekly Mean Pain Scores (Double-Blind Phase) Week 14 (n= 133, 122)	2.9 units on a scale Standard Deviation 1.64	3.1 units on a scale Standard Deviation 1.70
Weekly Mean Pain Scores (Double-Blind Phase) Week 15 (n= 131, 118)	2.9 units on a scale Standard Deviation 1.63	3.0 units on a scale Standard Deviation 1.64
Weekly Mean Pain Scores (Double-Blind Phase) Week 16 (n= 132, 118)	2.8 units on a scale Standard Deviation 1.65	3.0 units on a scale Standard Deviation 1.58
Weekly Mean Pain Scores (Double-Blind Phase) Week 18 (n= 128, 115)	2.8 units on a scale Standard Deviation 1.66	2.9 units on a scale Standard Deviation 1.73

SECONDARY outcome

Timeframe: Week 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least 1 dose of study treatment. Missing data were imputed using LOCF.

Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. Percentage of participants who had at least 30% and 50% pain reduction from SB baseline to Week 6 is reported. SB baseline refers to the last 7 pain diary entries up to and including Day 1.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=665 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Percentage of Participants With At Least 30 Percent and 50 Percent Reduction in Mean Pain Score (Single-Blind Phase) >=30 % Reduction	49.92 percentage of participants	—
Percentage of Participants With At Least 30 Percent and 50 Percent Reduction in Mean Pain Score (Single-Blind Phase) >=50 % Reduction	27.22 percentage of participants	—

SECONDARY outcome

Timeframe: Week 19

Population: FAS included all participants randomized to double-blind treatment who received at least 1 dose of double-blind study treatment. Missing data were imputed using LOCF.

Mean pain score was defined as the mean of the last 7 daily diary pain ratings. Participants rated their DPN pain over the past 24 hours on an 11-point numeric rating scale ranging from 0 = no pain to 10 = worst possible pain. A rating of 1-3 was considered as mild pain; 4-6 = moderate pain; and 7-10 = severe pain. Percentage of participants who had at least 30% and 50% pain reduction from SB baseline to Week 19 is reported.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Percentage of Participants With At Least 30 Percent and 50 Percent Reduction in Mean Pain Score (Double-Blind Phase) >=30% Reduction	82.99 percentage of participants	79.19 percentage of participants
Percentage of Participants With At Least 30 Percent and 50 Percent Reduction in Mean Pain Score (Double-Blind Phase) >=50% Reduction	62.59 percentage of participants	55.03 percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least one dose of study treatment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). Number of participants in each category are reported.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=620 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Patient Global Impression of Change (PGIC) (Single-Blind Phase) Minimally Improved	194 participants	—
Patient Global Impression of Change (PGIC) (Single-Blind Phase) No Change	65 participants	—
Patient Global Impression of Change (PGIC) (Single-Blind Phase) Minimally Worse	29 participants	—
Patient Global Impression of Change (PGIC) (Single-Blind Phase) Very Much Improved	93 participants	—
Patient Global Impression of Change (PGIC) (Single-Blind Phase) Much Improved	221 participants	—
Patient Global Impression of Change (PGIC) (Single-Blind Phase) Much Worse	15 participants	—
Patient Global Impression of Change (PGIC) (Single-Blind Phase) Very Much Worse	3 participants	—

SECONDARY outcome

Timeframe: Week 19

Population: FAS included all participants randomized to double-blind treatment who received at least 1 dose of double-blind study treatment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=138 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=134 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Patient Global Impression of Change (PGIC) (Double-Blind Phase) No Change	28 participants	20 participants
Patient Global Impression of Change (PGIC) (Double-Blind Phase) Minimally Worse	9 participants	6 participants
Patient Global Impression of Change (PGIC) (Double-Blind Phase) Much Worse	1 participants	8 participants
Patient Global Impression of Change (PGIC) (Double-Blind Phase) Very Much Worse	0 participants	3 participants
Patient Global Impression of Change (PGIC) (Double-Blind Phase) Very Much Improved	23 participants	23 participants
Patient Global Impression of Change (PGIC) (Double-Blind Phase) Much Improved	50 participants	46 participants
Patient Global Impression of Change (PGIC) (Double-Blind Phase) Minimally Improved	27 participants	28 participants

SECONDARY outcome

Timeframe: SB Baseline, Week 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least one dose of study medication. Here "n" signifies participants who were evaluable for specified time-point.

Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales: sleep disturbance (range 0-100), snoring (range 0-100), awaken short of breath (SOB) or with headache (range 0-100), sleep adequacy (range 0-100), somnolence (range: 0-100); sleep quantity (range: 0-24), optimal sleep (yes/no), and 9 item index measures of sleep disturbance provide composite scores: sleep problems index (range 0-100). Except adequacy, optimal sleep and quantity, higher scores=more impairment.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=665 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline: Sleep disturbance (n= 665)	53.6 units on a scale Standard Deviation 24.00	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline: Sleep Adequacy (n=665)	39.2 units on a scale Standard Deviation 23.22	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline: Snoring (n= 664)	44.7 units on a scale Standard Deviation 34.73	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline: Awaken SOB or With Headache (n=665)	18.9 units on a scale Standard Deviation 24.18	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline: Quantity of sleep (n=663)	5.9 units on a scale Standard Deviation 1.40	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline: Somnolence (n=665)	42.6 units on a scale Standard Deviation 23.49	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline: Sleep Problems Index (n=665)	49.2 units on a scale Standard Deviation 18.17	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6: Sleep disturbance (n= 621)	33.6 units on a scale Standard Deviation 24.31	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6: Snoring (n= 621)	39.9 units on a scale Standard Deviation 34.83	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6: Awaken SOB or With Headache (n= 621)	12.6 units on a scale Standard Deviation 22.64	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6: Quantity of sleep (n= 615)	6.6 units on a scale Standard Deviation 1.64	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6: Sleep Adequacy (n= 621)	52.6 units on a scale Standard Deviation 25.55	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6: Somnolence (n= 621)	34.2 units on a scale Standard Deviation 24.11	—
Medical Outcomes Study -Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6: Sleep Problems Index (n= 621)	34.4 units on a scale Standard Deviation 18.82	—

SECONDARY outcome

Timeframe: Week 19

Outcome measures

Outcome measures
Measure	Pregabalin DB n=138 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=134 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) Sleep Adequacy	59.2 units on a scale Standard Deviation 28.67	59.0 units on a scale Standard Deviation 27.67
Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) Somnolence	29.7 units on a scale Standard Deviation 24.39	30.6 units on a scale Standard Deviation 22.98
Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) Sleep Problems Index	28.5 units on a scale Standard Deviation 17.86	30.9 units on a scale Standard Deviation 18.59
Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) Sleep disturbance	26.6 units on a scale Standard Deviation 21.69	30.9 units on a scale Standard Deviation 23.05
Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) Snoring	41.9 units on a scale Standard Deviation 36.24	35.4 units on a scale Standard Deviation 35.95
Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) Awaken SOB or With Headache	12.3 units on a scale Standard Deviation 23.72	12.2 units on a scale Standard Deviation 23.89
Medical Outcomes Study -Sleep Scale (MOS-SS) (Double-Blind Phase) Quantity of sleep	6.7 units on a scale Standard Deviation 1.34	6.5 units on a scale Standard Deviation 1.47

SECONDARY outcome

Timeframe: SB Baseline, Week 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least one dose of study medication.

MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, and 9 item index measures of sleep disturbance provide composite scores: sleep problems index. Participants responded whether their sleep was optimal or not optimal by choosing yes or no.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=665 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) (Single-Blind Phase) SB Baseline	180 participants	—
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) (Single-Blind Phase) Week 6	266 participants	—

SECONDARY outcome

Timeframe: Week 19

Population: FAS included all participants randomized to double-blind treatment who received at least 1 dose of double-blind study treatment.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) (Double-Blind Phase)	67 participants	60 participants

SECONDARY outcome

Timeframe: SB Baseline, Week 1, 2, 3, 4, 5, 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least 1 dose of study treatment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for specified time point.

Weekly mean sleep interference score was defined as the mean of the daily sleep interference diary ratings split into 7 day intervals. Participants rated how painful DPN has interfered with their sleep during the past 24 hours on an 11-point numeric rating scale ranging from 0 = does not interfere with sleep to 10 = completely interferes (unable to sleep due to pain). SB baseline refers to the last 7 pain diary entries up to and including Day 1.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=663 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Weekly Mean Sleep Interference Score (Single-Blind Phase) Week 2 (n= 636)	4.5 units on a scale Standard Deviation 2.29	—
Weekly Mean Sleep Interference Score (Single-Blind Phase) SB Baseline (n= 663)	5.9 units on a scale Standard Deviation 2.09	—
Weekly Mean Sleep Interference Score (Single-Blind Phase) Week 1 (n= 657)	5.1 units on a scale Standard Deviation 2.22	—
Weekly Mean Sleep Interference Score (Single-Blind Phase) Week 3 (n= 614)	4.1 units on a scale Standard Deviation 2.30	—
Weekly Mean Sleep Interference Score (Single-Blind Phase) Week 4 (n= 589)	3.8 units on a scale Standard Deviation 2.30	—
Weekly Mean Sleep Interference Score (Single-Blind Phase) Week 5 (n= 566)	3.7 units on a scale Standard Deviation 2.29	—
Weekly Mean Sleep Interference Score (Single-Blind Phase) Week 6 (n= 548)	3.6 units on a scale Standard Deviation 2.35	—

SECONDARY outcome

Timeframe: DB Baseline, Week 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19

Outcome measures

Outcome measures
Measure	Pregabalin DB n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=147 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Weekly Mean Sleep Interference Score (Double-Blind Phase) DB Baseline (n= 147, 147)	2.5 units on a scale Standard Deviation 1.79	2.3 units on a scale Standard Deviation 1.66
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 7 (n= 144, 145)	2.6 units on a scale Standard Deviation 1.92	2.7 units on a scale Standard Deviation 1.99
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 8 (n= 143, 142)	2.6 units on a scale Standard Deviation 1.98	3.0 units on a scale Standard Deviation 1.98
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 9 (n= 140, 134)	2.3 units on a scale Standard Deviation 1.88	2.7 units on a scale Standard Deviation 1.94
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 10 (n= 138, 133)	2.3 units on a scale Standard Deviation 1.90	2.7 units on a scale Standard Deviation 1.98
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 11 (n= 138, 128)	2.2 units on a scale Standard Deviation 1.81	2.5 units on a scale Standard Deviation 1.78
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 12 (n= 136, 123)	2.3 units on a scale Standard Deviation 1.90	2.4 units on a scale Standard Deviation 1.84
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 13 (n= 134, 122)	2.3 units on a scale Standard Deviation 1.87	2.3 units on a scale Standard Deviation 1.78
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 14 (n= 133, 122)	2.3 units on a scale Standard Deviation 1.93	2.3 units on a scale Standard Deviation 1.80
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 15 (n= 132, 120)	2.4 units on a scale Standard Deviation 1.93	2.3 units on a scale Standard Deviation 1.80
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 16 (n= 132, 120)	2.3 units on a scale Standard Deviation 1.90	2.3 units on a scale Standard Deviation 1.77
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 17 (n= 129, 116)	2.2 units on a scale Standard Deviation 1.88	2.2 units on a scale Standard Deviation 1.85
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 18 (n= 128, 116)	2.3 units on a scale Standard Deviation 1.92	2.3 units on a scale Standard Deviation 1.85
Weekly Mean Sleep Interference Score (Double-Blind Phase) Week 19 (n= 121, 111)	2.3 units on a scale Standard Deviation 2.05	2.2 units on a scale Standard Deviation 1.80

SECONDARY outcome

Timeframe: Week 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least 1 dose of study treatment. Missing data were imputed using LOCF. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Endpoint mean sleep interference score was defined as the mean of the last 7 sleep interference diaries while receiving SB treatment. Participants rated how painful DPN has interfered with their sleep during the past 24 hours on an 11-point numeric rating scale ranging from 0 = does not interfere to 10 = completely interferes (unable to sleep due to pain).

Outcome measures

Outcome measures
Measure	Pregabalin DB n=658 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Endpoint Mean Sleep Interference Score (Single-Blind Phase)	3.8 units on a scale Standard Deviation 2.42	—

SECONDARY outcome

Timeframe: Week 19

Population: FAS included all participants randomized to double-blind treatment who received at least 1 dose of double-blind study treatment. Missing data were imputed using LOCF. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Endpoint mean sleep interference score was defined as the mean of the last 7 sleep interference diaries while receiving DB treatment. Participants rated how painful DPN has interfered with their sleep during the past 24 hours on an 11-point numeric rating scale ranging from 0 = does not interfere to 10 = completely interferes (unable to sleep due to pain).

Outcome measures

Outcome measures
Measure	Pregabalin DB n=138 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=132 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Endpoint Mean Sleep Interference Score (Double-Blind Phase)	2.4 units on a scale Standard Deviation 2.10	2.4 units on a scale Standard Deviation 2.05

SECONDARY outcome

Timeframe: SB Baseline, Week 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least 1 dose of study treatment. Here "n" signifies participants who were evaluable for specified time point.

QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. Consists of 5 domains: Physical functioning(Ph Fn)/large fiber (sum of item 8, 11, 13-15, 24, 27-35; range -4 to 56); Activities of daily living (sum of item 12, 22, 23, 25, 26; range 0 to 20); Symptoms (sum of item 1-7, 9; range 0 to 32); Small fiber (sum of item 10, 16, 17, 18; range 0 to 16); Autonomic (sum of item 19, 20, 21; range 0 to 12) and total QOL score (sum of items 1-35) range: -4 to 136. Higher score implied worse QOL.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=665 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) SB Baseline: Total QOL Scores (n= 665)	42.6 units on a scale Standard Deviation 22.22	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) SB Baseline: Ph Fn/Large Fiber (n= 665)	23.9 units on a scale Standard Deviation 13.07	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) SB Baseline: Activities of Daily Living (n= 665)	3.2 units on a scale Standard Deviation 3.69	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) SB Baseline: Symptoms (n= 665)	10.8 units on a scale Standard Deviation 5.55	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) SB Baseline: Small Fiber (n= 665)	3.4 units on a scale Standard Deviation 3.40	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) SB Baseline: Autonomic (n= 665)	1.3 units on a scale Standard Deviation 1.74	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) Week 6: Total QOL Scores (n= 618)	29.3 units on a scale Standard Deviation 21.76	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) Week 6: Ph Fn/Large Fiber (n= 618)	15.8 units on a scale Standard Deviation 12.62	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) Week 6: Activities of Daily Living (n= 618)	2.2 units on a scale Standard Deviation 3.08	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) Week 6: Symptoms (n= 618)	7.8 units on a scale Standard Deviation 5.72	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) Week 6: Small Fiber (n= 618)	2.3 units on a scale Standard Deviation 2.99	—
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Single-Blind Phase) Week 6: Autonomic (n= 618)	1.1 units on a scale Standard Deviation 1.69	—

SECONDARY outcome

Timeframe: Week 19

Outcome measures

Outcome measures
Measure	Pregabalin DB n=138 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=134 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Double-Blind Phase) Total QOL Scores	21.9 units on a scale Standard Deviation 20.02	24.1 units on a scale Standard Deviation 21.06
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Double-Blind Phase) Ph Fn/Large Fiber	11.4 units on a scale Standard Deviation 11.28	12.9 units on a scale Standard Deviation 12.72
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Double-Blind Phase) Activities of Daily Living	1.8 units on a scale Standard Deviation 2.85	1.8 units on a scale Standard Deviation 2.79
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Double-Blind Phase) Symptoms	6.1 units on a scale Standard Deviation 5.04	6.6 units on a scale Standard Deviation 5.29
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Double-Blind Phase) Small Fiber	1.8 units on a scale Standard Deviation 3.38	1.7 units on a scale Standard Deviation 2.50
Quality of Life Questionnaire- Diabetic Neuropathy (QOL-DN) (Double-Blind Phase) Autonomic	0.9 units on a scale Standard Deviation 1.55	1.1 units on a scale Standard Deviation 1.53

SECONDARY outcome

Timeframe: SB Baseline, Week 6

Participants rated their pain on a 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm = no pain to 100 mm = worst possible pain.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=665 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Pain Visual Analog Scale (VAS) (Single-Blind Phase) SB Baseline (n= 665)	68.1 mm Standard Deviation 13.79	—
Pain Visual Analog Scale (VAS) (Single-Blind Phase) Week 6 (n= 621)	39.8 mm Standard Deviation 23.19	—

SECONDARY outcome

Timeframe: Week 19

Participants rated their pain on a 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm = no pain to 100 mm = worst possible pain.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=138 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=134 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Pain Visual Analog Scale (VAS) (Double-Blind Phase)	25.3 mm Standard Deviation 20.98	30.1 mm Standard Deviation 23.44

SECONDARY outcome

Timeframe: SB Baseline, Week 6

BPI-sf: self-administered questionnaire developed to assess severity, impact of pain on daily functions, consisted of 5 questions. Questions 1-4 measured the severity of pain based on pain experienced over the past 24-hours on an 11-point scale ranged from 0 (no pain) to10 (worst possible pain). Question 5: 7 item subsets that measured level of interference of pain on daily functions on an 11-point scale ranged from 0 (does not interfere) to 10 (completely interferes).

Outcome measures

Outcome measures
Measure	Pregabalin DB n=665 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Brief Pain Inventory-Short Form (BPI-sf) (Single-Blind Phase) Week 6: Pain Interference (n= 637)	3.1 units on a scale Standard Deviation 2.31	—
Brief Pain Inventory-Short Form (BPI-sf) (Single-Blind Phase) SB Baseline: Pain Interference (n= 665)	5.2 units on a scale Standard Deviation 2.09	—
Brief Pain Inventory-Short Form (BPI-sf) (Single-Blind Phase) Week 6: Pain Severity (n= 637)	3.9 units on a scale Standard Deviation 2.13	—
Brief Pain Inventory-Short Form (BPI-sf) (Single-Blind Phase) SB Baseline: Pain Severity (n= 665)	6.1 units on a scale Standard Deviation 1.45	—

SECONDARY outcome

Timeframe: Week 19

Outcome measures

Outcome measures
Measure	Pregabalin DB n=140 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=136 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Brief Pain Inventory-Short Form (BPI-sf) (Double-Blind Phase) Pain Severity	2.6 units on a scale Standard Deviation 1.85	3.0 units on a scale Standard Deviation 2.03
Brief Pain Inventory-Short Form (BPI-sf) (Double-Blind Phase) Pain Interference	2.0 units on a scale Standard Deviation 2.05	2.4 units on a scale Standard Deviation 2.10

SECONDARY outcome

Timeframe: SB Baseline, Week 6

Population: SBAS included all participants who were enrolled into the single-blind treatment phase and received at least 1 dose of study treatment. Here "N" (number of participants) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for specified time point.

HADS: self-administered questionnaire, consists of 2 sub-scales; measuring anxiety (HADS-A), and depression (HADS-D). Each sub-scale consists of 7 items on which participants responded as to how each item applies to them on a 4-point scale ranging from 0 (no anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range for each sub-scale = 0 to 21, where higher score indicates more severe anxiety or depression.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=663 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Hospital Anxiety and Depression Scale (HADS) (Single-Blind Phase) SB Baseline: HADS-A (n= 663)	5.8 units on a scale Standard Deviation 3.95	—
Hospital Anxiety and Depression Scale (HADS) (Single-Blind Phase) SB Baseline: HADS-D (n= 663)	5.3 units on a scale Standard Deviation 3.70	—
Hospital Anxiety and Depression Scale (HADS) (Single-Blind Phase) Week 6: HADS-A (n= 616)	4.6 units on a scale Standard Deviation 3.54	—
Hospital Anxiety and Depression Scale (HADS) (Single-Blind Phase) Week 6: HADS-D (n= 616)	4.0 units on a scale Standard Deviation 3.52	—

SECONDARY outcome

Timeframe: Week 19

Outcome measures

Outcome measures
Measure	Pregabalin DB n=138 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=134 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Hospital Anxiety and Depression Scale (HADS) (Double-Blind Phase) HADS-A	3.8 units on a scale Standard Deviation 2.94	4.3 units on a scale Standard Deviation 3.56
Hospital Anxiety and Depression Scale (HADS) (Double-Blind Phase) HADS-D	3.3 units on a scale Standard Deviation 3.12	3.5 units on a scale Standard Deviation 3.28

SECONDARY outcome

Timeframe: Week 6

GESM: single-item, self-administered treatment satisfaction questionnaire. Participants answered "how would you rate the study medication you received for pain?" on a 7-point scale ranging from 1 (very satisfied) to 7 (very dissatisfied). Number of participants in each category are reported.

Outcome measures

Outcome measures
Measure	Pregabalin DB n=621 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) Slightly Satisfied	66 participants	—
Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) Neither Satisfied Nor Dissatisfied	71 participants	—
Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) Very Dissatisfied	19 participants	—
Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) Very Satisfied	241 participants	—
Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) Somewhat Satisfied	181 participants	—
Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) Slightly Dissatisfied	22 participants	—
Patient Global Evaluation of Study Medication (GESM) (Single-Blind Phase) Somewhat Dissatisfied	21 participants	—

SECONDARY outcome

Timeframe: Week 19

Outcome measures

Outcome measures
Measure	Pregabalin DB n=138 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=134 Participants Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) Very Satisfied	80 participants	64 participants
Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) Somewhat Satisfied	35 participants	36 participants
Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) Very Dissatisfied	2 participants	2 participants
Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) Slightly Satisfied	9 participants	14 participants
Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) Neither Satisfied Nor Dissatisfied	6 participants	10 participants
Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) Slightly Dissatisfied	5 participants	2 participants
Patient Global Evaluation of Study Medication (GESM) (Double-Blind Phase) Somewhat Dissatisfied	1 participants	6 participants

Adverse Events

Pregabalin SB

Serious events: 17 serious events

Other events: 331 other events

Deaths: 0 deaths

Pregabalin DB

Serious events: 11 serious events

Other events: 86 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pregabalin SB n=665 participants at risk Participants who were inadequately controlled on their current DPN treatment were switched to SB pregabalin capsules at a starting dose of 150 mg/day and increased to 300 mg/day, administered three times daily up to Week 6. Participants who experienced \>=30% pain reduction from baseline to Week 6 were eligible for DB treatment phase.	Pregabalin DB n=147 participants at risk Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=149 participants at risk Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Blood and lymphatic system disorders Anaemia	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Acute coronary syndrome	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Bradycardia	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Coronary artery disease	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial infarction	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.4% 2/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vitreous haemorrhage	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Rectal haemorrhage	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Generalised oedema	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Non-cardiac chest pain	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholelithiasis	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Gangrene	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Osteomyelitis	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.45% 3/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Sepsis	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Tracheitis	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urosepsis	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Burns first degree	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Femoral neck fracture	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Road traffic accident	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood pressure increased	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetic complication	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Ketoacidosis	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebrovascular accident	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Presyncope	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Transient ischaemic attack	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Pregabalin SB n=665 participants at risk Participants who were inadequately controlled on their current DPN treatment were switched to SB pregabalin capsules at a starting dose of 150 mg/day and increased to 300 mg/day, administered three times daily up to Week 6. Participants who experienced \>=30% pain reduction from baseline to Week 6 were eligible for DB treatment phase.	Pregabalin DB n=147 participants at risk Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received pregabalin capsules 150 mg/day or 300 mg/day, administered three times daily up to Week 19 during DB treatment phase.	Placebo n=149 participants at risk Participants who experienced \>=30% pain reduction in SB treatment phase, after Week 6 received matching placebo capsules, administered three times daily up to Week 19 during DB treatment phase.
Renal and urinary disorders Urine odour abnormal	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Erectile dysfunction	0.45% 3/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	0.45% 3/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.60% 4/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.3% 2/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.4% 2/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Eosinophilia	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Arrhythmia	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Coronary artery disease	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Extrasystoles	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	0.30% 2/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Tinnitus	0.45% 3/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	0.75% 5/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.3% 2/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Cataract	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Conjunctivitis	0.45% 3/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Cystoid macular oedema	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Diplopia	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Dry eye	0.30% 2/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye haemorrhage	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye pain	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Periorbital oedema	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Retinal haemorrhage	0.30% 2/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Retinal oedema	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Retinopathy hypertensive	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	1.8% 12/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Visual impairment	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vitreous disorder	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vitreous haemorrhage	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal discomfort	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.68% 1/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	2.3% 15/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.4% 2/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 3/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dental caries	0.15% 1/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.67% 1/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	2.3% 15/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.4% 5/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.0% 6/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	1.8% 12/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.4% 5/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 3/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	0.30% 2/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Flatulence	0.60% 4/665 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/147 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/149 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.