Trial Outcomes & Findings for Randomized, Double-Blind, Multicenter, Placebo-Controlled Study Of Pregabalin For Pain Associated With Diabetic Peripheral Neuropathy (NCT NCT00553475)

NCT ID: NCT00553475

Last Updated: 2021-01-25

Results Overview

Change from baseline: Score at study endpoint minus score at baseline. Study endpoint is defined as the mean of the last seven entries of the daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) while on study medication up to and including day after last dose.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 314 participants
• Primary outcome timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)
• Results posted on: 2021-01-25

Participant Flow

After a 1-week baseline phase, subjects were classified into 2 strata based on creatinine clearance (CLcr) values (Low: 30 <CLcr <=60 mL/minute; Normal: CLcr > 60 mL/minute) and were each randomly assigned to 1 of 3 treatment groups.

Participant milestones

Measure	Placebo During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Overall Study STARTED	135	134	45
Overall Study COMPLETED	119	114	32
Overall Study NOT COMPLETED	16	20	13

Reasons for withdrawal

Measure	Placebo During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Overall Study Adverse Event	7	17	13
Overall Study Lack of Efficacy	7	1	0
Overall Study Withdrawal by Subject	1	1	0
Overall Study Physician Decision	1	0	0
Overall Study Due to moving	0	1	0

Baseline Characteristics

Randomized, Double-Blind, Multicenter, Placebo-Controlled Study Of Pregabalin For Pain Associated With Diabetic Peripheral Neuropathy

Baseline characteristics by cohort

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.	Total n=314 Participants Total of all reporting groups
Age, Customized < 18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Age, Customized 18 - 44 years	7 participants n=5 Participants	8 participants n=7 Participants	1 participants n=5 Participants	16 participants n=4 Participants
Age, Customized 45 - 64 years	76 participants n=5 Participants	78 participants n=7 Participants	25 participants n=5 Participants	179 participants n=4 Participants
Age, Customized >= 65 years	52 participants n=5 Participants	48 participants n=7 Participants	19 participants n=5 Participants	119 participants n=4 Participants
Age, Continuous	61.3 years STANDARD_DEVIATION 9.6 • n=5 Participants	61.3 years STANDARD_DEVIATION 10.3 • n=7 Participants	62.2 years STANDARD_DEVIATION 10.3 • n=5 Participants	61.4 years STANDARD_DEVIATION 10.0 • n=4 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	32 Participants n=7 Participants	13 Participants n=5 Participants	77 Participants n=4 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	102 Participants n=7 Participants	32 Participants n=5 Participants	237 Participants n=4 Participants
Region of Enrollment Japan	135 participants n=5 Participants	134 participants n=7 Participants	45 participants n=5 Participants	314 participants n=4 Participants

PRIMARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

Change from baseline: Score at study endpoint minus score at baseline. Study endpoint is defined as the mean of the last seven entries of the daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) while on study medication up to and including day after last dose.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline to Study Endpoint in Mean Weekly Pain Scores	-1.20 score on scale Standard Error 0.21	-1.82 score on scale Standard Error 0.22	-1.94 score on scale Standard Error 0.32

PRIMARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

Change from baseline: Score at study endpoint minus score at baseline. Study endpoint is defined as the mean of the last seven entries of the daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) while on study medication up to and including day after last dose. Subjects are classified by exposure to pregabalin, which is estimated by creatinine clearance (CLcr).

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=120 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=59 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline to Study Endpoint in Mean Weekly Pain Scores by Groups of Subjects With Expected Similar Plasma Concentrations	-1.27 score on scale Standard Error 0.16	-1.93 score on scale Standard Error 0.17	-1.90 score on scale Standard Error 0.25

PRIMARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

A responder is defined as a subject with a 50% reduction in weekly mean pain score from baseline to study endpoint.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Number of Responders	29 participants	39 participants	16 participants

PRIMARY outcome

Timeframe: From baseline to Week 1

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 1.

Change from baseline: Score at Week 1 minus score at baseline

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 1 in Mean Weekly Pain Scores	-0.39 score on scale Standard Error 0.17	-0.82 score on scale Standard Error 0.17	-1.14 score on scale Standard Error 0.26

PRIMARY outcome

Timeframe: From baseline to Week 2

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 2.

Change from baseline: Score at Week 2 minus score at baseline

Outcome measures

Measure	Placebo n=133 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=132 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=41 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 2 in Mean Weekly Pain Scores	-0.57 score on scale Standard Error 0.17	-1.17 score on scale Standard Error 0.17	-1.80 score on scale Standard Error 0.26

PRIMARY outcome

Timeframe: From baseline to Week 3

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 3.

Change from baseline: Score at Week 3 minus score at baseline

Outcome measures

Measure	Placebo n=131 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=129 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=41 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 3 in Mean Weekly Pain Scores	-0.80 score on scale Standard Error 0.17	-1.40 score on scale Standard Error 0.17	-1.93 score on scale Standard Error 0.26

PRIMARY outcome

Timeframe: From baseline to Week 4

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 4.

Change from baseline: Score at Week 4 minus score at baseline

Outcome measures

Measure	Placebo n=130 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=128 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=41 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 4 in Mean Weekly Pain Scores	-0.89 score on scale Standard Error 0.17	-1.53 score on scale Standard Error 0.17	-2.00 score on scale Standard Error 0.26

PRIMARY outcome

Timeframe: From baseline to Week 5

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 5.

Change from baseline: Score at Week 5 minus score at baseline

Outcome measures

Measure	Placebo n=130 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=125 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=38 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 5 in Mean Weekly Pain Scores	-0.91 score on scale Standard Error 0.17	-1.57 score on scale Standard Error 0.17	-2.07 score on scale Standard Error 0.27

PRIMARY outcome

Timeframe: From baseline to Week 6

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 6.

Change from baseline: Score at Week 6 minus score at baseline

Outcome measures

Measure	Placebo n=128 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=125 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=37 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 6 in Mean Weekly Pain Scores	-0.94 score on scale Standard Error 0.17	-1.72 score on scale Standard Error 0.17	-2.06 score on scale Standard Error 0.27

PRIMARY outcome

Timeframe: From baseline to Week 7

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 7.

Change from baseline: Score at Week 7 minus score at baseline

Outcome measures

Measure	Placebo n=125 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=124 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=36 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 7 in Mean Weekly Pain Scores	-1.04 score on scale Standard Error 0.17	-1.76 score on scale Standard Error 0.17	-2.13 score on scale Standard Error 0.27

PRIMARY outcome

Timeframe: From baseline to Week 8

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 8.

Change from baseline: Score at Week 8 minus score at baseline

Outcome measures

Measure	Placebo n=125 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=123 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=36 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 8 in Mean Weekly Pain Scores	-1.18 score on scale Standard Error 0.17	-1.85 score on scale Standard Error 0.17	-2.12 score on scale Standard Error 0.27

PRIMARY outcome

Timeframe: From baseline to Week 9

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 9.

Change from baseline: Score at Week 9 minus score at baseline

Outcome measures

Measure	Placebo n=123 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=121 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=35 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 9 in Mean Weekly Pain Scores	-1.20 score on scale Standard Error 0.17	-1.93 score on scale Standard Error 0.17	-2.06 score on scale Standard Error 0.28

PRIMARY outcome

Timeframe: From baseline to Week 10

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 10.

Change from baseline: Score at Week 10 minus score at baseline

Outcome measures

Measure	Placebo n=122 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=118 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=33 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 10 in Mean Weekly Pain Scores	-1.23 score on scale Standard Error 0.17	-1.93 score on scale Standard Error 0.18	-2.10 score on scale Standard Error 0.28

PRIMARY outcome

Timeframe: From baseline to Week 11

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 11.

Change from baseline: Score at Week 11 minus score at baseline

Outcome measures

Measure	Placebo n=121 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=116 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=33 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 11 in Mean Weekly Pain Scores	-1.32 score on scale Standard Error 0.17	-1.95 score on scale Standard Error 0.18	-2.09 score on scale Standard Error 0.28

PRIMARY outcome

Timeframe: From baseline to Week 12

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 12.

Change from baseline: Score at Week 12 minus score at baseline

Outcome measures

Measure	Placebo n=120 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=116 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=33 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 12 in Mean Weekly Pain Scores	-1.36 score on scale Standard Error 0.17	-2.01 score on scale Standard Error 0.18	-2.13 score on scale Standard Error 0.29

PRIMARY outcome

Timeframe: From baseline to Week 13

Population: Full analysis set. Observed case (No imputation).

The mean change from baseline in mean weekly pain score from daily pain diary using the 11-point numerical rating scale 0(no pain) to 10(worst possible pain) at Week 13.

Change from baseline: Score at Week 13 minus score at baseline

Outcome measures

Measure	Placebo n=119 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=115 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=33 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline at Week 13 in Mean Weekly Pain Scores	-1.38 score on scale Standard Error 0.17	-2.04 score on scale Standard Error 0.18	-2.12 score on scale Standard Error 0.29

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Physical Functioning	2.70 score on scale Standard Error 1.58	2.43 score on scale Standard Error 1.59	3.86 score on scale Standard Error 2.33

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Role Limitations-Physical	4.38 score on scale Standard Error 2.47	2.28 score on scale Standard Error 2.50	3.97 score on scale Standard Error 3.70

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Bodily Pain	10.34 score on scale Standard Error 1.97	11.84 score on scale Standard Error 1.99	12.89 score on scale Standard Error 2.91

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: General Health Perception	2.31 score on scale Standard Error 1.44	3.29 score on scale Standard Error 1.45	4.40 score on scale Standard Error 2.14

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Social Functioning	3.00 score on scale Standard Error 2.39	8.06 score on scale Standard Error 2.41	11.16 score on scale Standard Error 3.54

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Role Limitations-Emotional	4.13 score on scale Standard Error 2.52	5.05 score on scale Standard Error 2.55	6.35 score on scale Standard Error 3.77

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Vitality	5.28 score on scale Standard Error 1.92	4.20 score on scale Standard Error 1.94	12.87 score on scale Standard Error 2.84

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form 36-Item Health Survey Scores at study endpoint. Short-Form 36-Item Health Survey is scored from 0-100 with higher scores reflecting better patient status.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short Form 36-Item (SF-36) Health Survey: Mental Health	3.84 score on scale Standard Error 1.83	5.33 score on scale Standard Error 1.85	7.81 score on scale Standard Error 2.72

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in the weekly mean sleep interference score at study endpoint. Score range is from 0-10. Higher scores indicate more severe interference with sleep.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Mean Sleep Interference Scores	-0.74 score on scale Standard Error 0.18	-1.59 score on scale Standard Error 0.18	-1.36 score on scale Standard Error 0.27

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Sensory score ranges from 0-33. Higher scores indicate more severe pain.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short-Form McGill Pain Questionnaire: Sensory Scores	-2.82 score on scale Standard Error 0.50	-4.60 score on scale Standard Error 0.50	-4.95 score on scale Standard Error 0.74

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Affective score ranges from 0-12. Higher scores indicate more severe pain.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short-Form McGill Pain Questionnaire: Affective Scores	-0.83 score on scale Standard Error 0.20	-1.43 score on scale Standard Error 0.20	-1.39 score on scale Standard Error 0.30

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Total score ranges from 0-45. Higher scores indicate more severe pain.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short-Form McGill Pain Questionnaire: Total Scores	-3.68 score on scale Standard Error 0.66	-6.03 score on scale Standard Error 0.66	-6.36 score on scale Standard Error 0.97

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Visual Analogue Scale Score ranges from 0-100 mm. Higher scores indicate more severe pain.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short-Form McGill Pain Questionnaire: Visual Analogue Scale Scores	-16.92 mm Standard Error 2.38	-24.19 mm Standard Error 2.40	-24.41 mm Standard Error 3.53

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Short-Form McGill Pain Questionnaire Scores at study endpoint. Present pain intensity score ranges from 0-5. Higher scores indicate more severe pain.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Short-Form McGill Pain Questionnaire: Present Pain Intensity Scores	-0.59 score on scale Standard Error 0.09	-0.80 score on scale Standard Error 0.09	-0.96 score on scale Standard Error 0.13

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep disturbance ranges from 0-100. Higher scores indicate more severe pain.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Disturbance	-9.03 score on scale Standard Error 1.86	-15.40 score on scale Standard Error 1.88	-12.81 score on scale Standard Error 2.77

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for snoring ranges from 0-100. Higher scores indicate more of the attribute.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Snoring	-6.00 score on scale Standard Error 2.51	-5.96 score on scale Standard Error 2.53	-1.56 score on scale Standard Error 3.71

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep shortness of breath or headache ranges from 0-100. Higher scores indicate more of the attribute.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Shortness of Breath or Headache	-1.63 score on scale Standard Error 1.69	-3.02 score on scale Standard Error 1.71	-4.47 score on scale Standard Error 2.51

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for quantity of sleep ranges from 0-24. Higher scores indicate more of the attribute named in the subscale.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Quantity of Sleep	0.37 score on scale Standard Error 0.12	0.69 score on scale Standard Error 0.12	0.54 score on scale Standard Error 0.18

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for sleep adequacy ranges from 0-100. Higher scores indicate more of the attribute.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Sleep Adequacy	12.08 score on scale Standard Error 2.61	17.69 score on scale Standard Error 2.64	21.73 score on scale Standard Error 3.87

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for somnolence ranges from 0-100. Higher scores indicate more of the attribute.

Outcome measures

Measure	Placebo n=134 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Somnolence	-2.96 score on scale Standard Error 2.17	0.83 score on scale Standard Error 2.19	4.83 score on scale Standard Error 3.20

SECONDARY outcome

Timeframe: From baseline to Week 13 or up to study discontinuation (Study Endpoint)

Population: Full analysis set. Last observation carried forward.

The mean change from baseline in Medical Outcomes Study - Sleep Scale Scores at study endpoint. Score for overall sleep problems index ranges from 0-100. Higher scores indicate more of the attribute.

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Change From Baseline in Medical Outcomes Study (MOS) - Sleep Scale: Overall Sleep Problems Index	-7.91 score on scale Standard Error 1.45	-11.45 score on scale Standard Error 1.46	-9.73 score on scale Standard Error 2.16

SECONDARY outcome

Timeframe: Week 13 or up to discontinuation

Population: Full analysis set. Last observation carried forward.

Clinical Global Impression of Change is a clinician-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Clinical Global Impression of Change	3.3 score on scale Standard Deviation 1.2	2.9 score on scale Standard Deviation 1.1	2.7 score on scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Week 13 or up to discontinuation

Population: Full analysis set. Last observation carried forward.

The Patient Global Impression of Change is a patient-rated instrument that measures change in patient's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Measure	Placebo n=135 Participants During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=133 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 Participants During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Patient Global Impression of Change	3.4 score on scale Standard Deviation 1.3	3.2 score on scale Standard Deviation 1.0	2.8 score on scale Standard Deviation 1.0

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 50 other events

Deaths: 0 deaths

Pregabalin 300 mg/Day

Serious events: 2 serious events

Other events: 71 other events

Deaths: 0 deaths

Pregabalin 600 mg/Day

Serious events: 1 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=135 participants at risk During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 participants at risk During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 participants at risk During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Cardiac disorders Atrial fibrillation	0.74% 1/135	0.00% 0/134	0.00% 0/45
Gastrointestinal disorders Nausea	0.74% 1/135	0.00% 0/134	0.00% 0/45
General disorders Feeling abnormal	0.74% 1/135	0.00% 0/134	0.00% 0/45
General disorders Peripheral coldness	0.74% 1/135	0.00% 0/134	0.00% 0/45
General disorders Pyrexia	0.00% 0/135	0.75% 1/134	0.00% 0/45
Infections and infestations Herpes zoster	0.74% 1/135	0.00% 0/134	0.00% 0/45
Metabolism and nutrition disorders Dehydration	0.00% 0/135	0.00% 0/134	2.2% 1/45
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/135	0.00% 0/134	2.2% 1/45
Nervous system disorders Brain stem infarction	0.00% 0/135	0.75% 1/134	0.00% 0/45
Nervous system disorders Hypertensive encephalopathy	0.00% 0/135	0.75% 1/134	0.00% 0/45
Nervous system disorders Hypoaesthesia	0.74% 1/135	0.00% 0/134	0.00% 0/45

Other adverse events

Measure	Placebo n=135 participants at risk During a 13-week double-blind phase, subjects received matching placebo.	Pregabalin 300 mg/Day n=134 participants at risk During a 13-week double-blind phase, after 1 week of up titration, subjects received pregabalin 300 mg/day for 12 weeks.	Pregabalin 600 mg/Day n=45 participants at risk During a 13-week double-blind phase, after 1 week of up titration, subjects with low CLcr received pregabalin 300 mg/day and subjects with normal CLcr received pregabalin 600 mg/day for 12 weeks.
Gastrointestinal disorders Constipation	0.74% 1/135	3.0% 4/134	6.7% 3/45
Gastrointestinal disorders Diarrhoea	3.7% 5/135	2.2% 3/134	6.7% 3/45
General disorders Oedema	0.74% 1/135	3.0% 4/134	6.7% 3/45
General disorders Oedema peripheral	5.9% 8/135	14.2% 19/134	17.8% 8/45
Infections and infestations Nasopharyngitis	14.8% 20/135	11.9% 16/134	8.9% 4/45
Investigations Weight increased	3.7% 5/135	12.7% 17/134	15.6% 7/45
Nervous system disorders Dizziness	6.7% 9/135	19.4% 26/134	40.0% 18/45
Nervous system disorders Somnolence	8.9% 12/135	20.9% 28/134	40.0% 18/45

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.govCallCenter@pfizer.com

Results disclosure agreements

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

Restriction type: OTHER