Placebo-controlled Safety and Efficacy Study of Pregabalin in Subjects With Post-traumatic Peripheral Neuropathic Pain

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01701362
• Collaborator: (none)
• Enrollment: 542
• Locations: 156
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is designed to investigate if pregabalin is effective in treating neuropathic (nerve) pain resulting from peripheral nerve trauma due to a traumatic or surgical event such as, for example, motor vehicle accident, fall, sports injury, knee or hip replacement, hernia repair, thoracotomy, mastectomy, focal/localized burns or crush injury.

Condition or Disease	Intervention/Treatment	Phase
Neuropathic Pain	Drug: pregabalin; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 542 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Double Blind Placebo Controlled Parallel Group Study Of The Efficacy And Safety Of Pregabalin (Bid) In Subjects With Post-traumatic Peripheral Neuropathic Pain
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: pregabalin	Drug: pregabalin; capsules, 150-600 mg/day administered in divided doses twice a day for 15 weeks after randomization; Other Names: Lyrica, PD-144723
Placebo Comparator: placebo	Drug: placebo; capsules, placebo for pregabalin administered in divided doses twice a day for 15 weeks after randomization

Outcome Measures

Primary Outcome Measures

1. Baseline Mean Pain Score [Baseline]

   This is based on the daily pain dairy and is defined as the baseline mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10.

2. Change From Baseline to Week 15 in Weekly Mean Pain Score [up to Week 15]

   This is based on the daily pain diary and is defined as the change from baseline to week 15 in mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10.

Secondary Outcome Measures

1. Patient Global Impression of Change (PGIC) at Week 15 [Week 15]

   A self administered instrument that measures changes in participants' overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). The PGIC is based on the Clinical Global Impression of Change, which is a validated scale.

2. Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS) [up to Week 15]

   This is an 11-point NRS ranging from 0 ("pain does not interfere with sleep") to 10 ("pain completely interferes with sleep" [unable to sleep due to pain]). Participants describe how pain has interfered with their sleep during the past 24 hours. Please note that the data for Baseline (raw scores) have been included in the below table to read the change from Baseline data in context. Note: Weekly mean SIRS scores were derived from the daily sleep diary and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean SIRS scores were defined as the mean of the 7 daily diary SIRS scores from Day 2+7 (n-1) to Day 1+7*n. For participants with multiple diary scores collected on the same day, the average of all non-missing scores for that day was used in any analyses or data listings. "Overall" is the pooled average sleep interference score for each subject across all post-baseline/randomization weeks.

3. Change From Baseline in Pain Severity Index (Brief Pain Inventory-short Form [BPI-sf]) [Week 15]

   A self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. The BPI-sf consists of 5 questions. Four items measure pain on 11-point response scales from 0 (No Pain) to 10 (Pain as bad as you can imagine). In the above scale, score 0 indicates the better outcome whereas score 10 indicates the worse outcome.

4. Change From Baseline in Pain Interference Index (BPI-sf) [Week 15]

   BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. It consists of 7 sub-questions that evaluates the level of pain interference with daily functioning on 11-point response scales from 0 (does not interfere) to 10 (completely interferes). The BPI-sf pain interference index was calculated as average of the seven individual pain interference scores.

5. Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores [Week 15]

   A self-administered questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression. Each dimension is rated on a 3 point response scale and the scores are combined to form a single index value between 0 and 1 with higher scores being more positive (better health status). The EQ-5D was completed by the subject at week-0 and week-15/ET where 30% responder and 50% responder status would be defined for each participants based on the percent change from baseline (week 0/Randomization) to each visit week in mean pain score and participant global impression of change (PGIC). PGIC is a self-administered instrument that measures change in participant's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). It is based on the Clinical Global Impression of Change CGIC), which is a validated scale.

6. Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score. [Baseline]

   MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours.

7. Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score. [Week 15]

   MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours.

8. Percentage of Participants in MOS-SS With Optimal Sleep Status. [Week 15]

   MOS-SS optimal sleep status analyzed on a scale of four parameters: any improvements, no change, any worsening and not applicable.

9. Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%. [Week 15]

   Participants with at least 30% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain.

10. Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50% [Week 15]

    Participants with at least 50% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have chronic peripheral neuropathic pain present for than 6 months after a traumatic or surgical event such as, for example, motor vehicle accident, fall, sports injury, knee or hip replacement, hernia repair, thoracotomy, mastectomy, focal/localized burns or crush injury.

• Subjects must be literate and have the ability (unaided) to understand and use the interactive voice response system (IVRS), have daily access to a telephone in order to complete the IVRS assessments each day, perform telephone visits and complete all required assessments/forms.

• Subjects must have sufficient post-traumatic neuropathic pain at screening and baseline.

Exclusion Criteria:

• Subjects with neuropathic pain due to diabetic peripheral neuropathy (DPN), post herpetic neuralgia (PHN), HIV, trigeminal neuralgia (TGN), carpal tunnel syndrome (CTS) or with central neuropathic pain (for example, due to spinal cord injury) or with Complex Regional Pain Syndrome (CRPS, Type I or Type II).

• Subjects with other pain that may confound assessment or self-evaluation of the peripheral neuropathic pain.

• Subjects who have failed pregabalin treatment due to lack of efficacy with an adequate course of therapy at doses greater than or equal to 150 mg/day, who have previously participated in a pregabalin clinical trial or who have been treated with pregabalin at any time during the 6 month period prior to screening.

• Subjects with epilepsy; pernicious anemia; hematological illnesses; known HIV infection; any clinically unstable cardiovascular (including a myocardial infarction [heart attack] in the 3 months prior to screening), hematological, autoimmune, endocrine, renal, hepatic (including chronic hepatitis B, hepatitis B within the 3 months prior to screening) respiratory, or gastrointestinal disease; symptomatic peripheral vascular disease including intermittent claudication; uncontrolled diabetes mellitus; untreated hypothyroidism.

• Subjects with a diagnosis of DSM-IV TR Axis I disorder (including, for example, schizophrenia, bipolar disorder) with the exceptions of Generalized Anxiety Disorder (GAD) or major depression that is clinically stable.

• Subjects considered at risk of suicide or self-harm based on investigator judgment and/or details of a risk assessment.

• Use of prohibited medications in the absence of appropriate washout periods.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennesse Valley Pain Consultants	Huntsville	Alabama	United States	35801
2	Dedicated Clinical Research	Goodyear	Arizona	United States	85395
3	Elite Clinical Studies, LLC	Phoenix	Arizona	United States	85018
4	HOPE Research Institute	Phoenix	Arizona	United States	85018
5	The Pain Center of Arizona	Phoenix	Arizona	United States	85018
6	Arizona Research Center	Phoenix	Arizona	United States	85023
7	The Pain Center of Arizona	Phoenix	Arizona	United States	85027
8	Neuromuscular Research Center	Phoenix	Arizona	United States	85028
9	Quality of Life Medical & Research Centers, LLC	Tucson	Arizona	United States	85712
10	Advanced Rx Clinical Research	Artesia	California	United States	90701
11	Behavioral Research Specialists, LLC	Glendale	California	United States	91206
12	NervePro Medical Corp.	Irvine	California	United States	92618
13	University of California, Irvine	Irvine	California	United States	92697
14	Clinical and Translational Research Institute	La Jolla	California	United States	92093
15	Alliance Research Centers	Laguna Hills	California	United States	92653
16	South Orange County Surgical Medical Group	Laguna Hills	California	United States	92653
17	Center For United Research, Inc.	Lakewood	California	United States	90805
18	University of Southern California	Los Angeles	California	United States	90033
19	USC I.D.S. Pharmacy	Los Angeles	California	United States	90089
20	Samaritan Center for Medical Research	Los Gatos	California	United States	95032
21	North County Clinical Research	Oceanside	California	United States	92056
22	Allied Clinical Research	Roseville	California	United States	95661
23	Northern California Research	Sacramento	California	United States	95821
24	Diablo Clinical Research, Inc.	Walnut Creek	California	United States	94598
25	Elite Clinical Trials, Inc.	Wildomar	California	United States	92595
26	Colorado Clinic	Boulder	Colorado	United States	80301
27	Mountain View Clinical Research Inc.	Denver	Colorado	United States	80209
28	St. Luke's Medical Clinic	Fort Collins	Colorado	United States	80525
29	Investigational Drug Services, The George Washington University Medical Center	Washington	District of Columbia	United States	20037
30	The George Washington University Medical Center (Department of Neurology)	Washington	District of Columbia	United States	20037
31	The George Washington University Medical Center	Washington	District of Columbia	United States	20037
32	Orthopedic Research Institute	Boynton Beach	Florida	United States	33472
33	Advance Medical Research	Clearwater	Florida	United States	33756
34	Innovative Research of West Florida	Clearwater	Florida	United States	33756
35	Aga Clinical Trials	Hialeah	Florida	United States	33012
36	Health Care Family Rehab & Research Center	Hialeah	Florida	United States	33012
37	Research in Miami, Inc.	Hialeah	Florida	United States	33013
38	Homestead Medical Research , Inc.	Homestead	Florida	United States	33030
39	AMPM Research Clinic	Miami Gardens	Florida	United States	33169
40	San Marcus Research Clinic, Inc.	Miami	Florida	United States	33015
41	Advanced Pharma CR, LLC	Miami	Florida	United States	33136
42	Florida International Research Center	Miami	Florida	United States	33173
43	Kendall South Medical Center, Inc.	Miami	Florida	United States	33185
44	Compass Research, LLC	Orlando	Florida	United States	32806
45	A-One Family Practice	Ormond Beach	Florida	United States	32174
46	Aba Family Medicine, LLC	Ormond Beach	Florida	United States	32174
47	Ribo Research, LLC dba Peninsula Resarch	Ormond Beach	Florida	United States	32174
48	Comprehensive Pain Care of South Florida	Royal Palm Beach	Florida	United States	33411
49	Sarasota Pain Medicine Research	Sarasota	Florida	United States	34238
50	Meridien Research	Tampa	Florida	United States	33634
51	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
52	Columbus Regional Research Institute	Columbus	Georgia	United States	31904
53	Georgia Institute for Clinical Research, LLC	Marietta	Georgia	United States	30060
54	Advanced Internal Medicine, PC	Stockbridge	Georgia	United States	30281
55	Research 1 Clinical Research Network, Inc. (Administrative Office Only)	Stockbridge	Georgia	United States	30281
56	Rehabilitation Institute of Chicago	Chicago	Illinois	United States	60611
57	Chicago Anesthesia Associates	Chicago	Illinois	United States	60657
58	Kansas City Bone & Joint Clinic	Overland Park	Kansas	United States	66211
59	Otri-Med Corporation	Edgewood	Kentucky	United States	41017
60	Central Kentucky Research Associates, Inc.	Lexington	Kentucky	United States	40509
61	Centex Studies, Inc	Lake Charles	Louisiana	United States	70601
62	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
63	Michigan Head Pain and Neurological Institute	Ann Arbor	Michigan	United States	48104
64	Medex Healthcare Research, Inc.	Saint Louis	Missouri	United States	63117
65	Quality Clinical Research, Inc.	Omaha	Nebraska	United States	68114
66	Heartland Clinical Research, Inc.	Omaha	Nebraska	United States	68134
67	Advanced Biomedical Research of America	Las Vegas	Nevada	United States	89123
68	University of Rochester, Translational Pain Research	Rochester	New York	United States	14618
69	PMG Research of Charlotte	Charlotte	North Carolina	United States	28209
70	PMG Research of Winston-Salem	Winston-Salem	North Carolina	United States	27103
71	Northern Ohio Neurosciences, LLC	Bellevue	Ohio	United States	44811
72	Wells Institute for Health Awareness	Kettering	Ohio	United States	45429
73	Northwest Ohio Research Center, LLC	Toledo	Ohio	United States	43623
74	Robert L Kalb, M.D, Inc	Toledo	Ohio	United States	43623
75	Cor Clinical Research, Llc	Oklahoma City	Oklahoma	United States	73103
76	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
77	Summit Research Network, Inc.	Portland	Oregon	United States	97210
78	Allegheny Pain Management, P.C.	Altoona	Pennsylvania	United States	16602
79	CRI Lifetree	Philadelphia	Pennsylvania	United States	19139
80	Pharmacorp Clinical Trials, Inc.	Charleston	South Carolina	United States	29412
81	TLM Medical Services, LLC	Columbia	South Carolina	United States	29204
82	Piedmont Comprehensive Pain Management Group, LLC	Greenville	South Carolina	United States	29601
83	Pharmacum Biomedical Research	Greenville	South Carolina	United States	29605
84	New Phase Research and Development	Knoxville	Tennessee	United States	37919
85	Dallas Pain Consultants	Dallas	Texas	United States	75203
86	FutureSearch Trials of Dallas, L. P.	Dallas	Texas	United States	75231
87	Abigail R. Neiman, MD, PA	Houston	Texas	United States	77024
88	Agadadash Kuliev, MD, PA	Houston	Texas	United States	77043
89	Biopharma Informatic Inc. Research Center	Houston	Texas	United States	77043
90	Medstar Clinical Research Associates	Houston	Texas	United States	77083
91	ClinRx Research, LLC	Richardson	Texas	United States	75080
92	DCT - Stone Oak, LLC dba Discovery Clinical Trials	San Antonio	Texas	United States	78258
93	Sealy Urgent Care Center and Medical Clinic	Sealy	Texas	United States	77474
94	Grayline Clinical Drug Trials	Wichita Falls	Texas	United States	76309
95	Lifetree Clinical Research	Salt Lake City	Utah	United States	84106
96	J. Lewis Research, Inc./Foothill Family Clinic	Salt Lake City	Utah	United States	84109
97	J. Lewish Research, Inc./Foothill Family Clinic South	Salt Lake City	Utah	United States	84121
98	Integrated Neurology Services , PLLC	Arlington	Virginia	United States	22205
99	IntegraTrials, LLC	Arlington	Virginia	United States	22205
100	Washington Center for Pain Management LLC	Bellevue	Washington	United States	98004
101	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
102	Washington Center for Pain Management LLC	Edmonds	Washington	United States	98026
103	Washington Center for Pain Management LLC	Everett	Washington	United States	98201
104	Washington Center for Pain Management LLC	Renton	Washington	United States	98055
105	Summit Research Network (Seattle) LLC	Seattle	Washington	United States	98104
106	MHAT Puls AD	Blagoevgrad		Bulgaria	2700
107	MHAT "Avis Medika"	Pleven		Bulgaria	5800
108	MHAT "Sv.Pantaleymon"	Pleven		Bulgaria	5800
109	DCC Akta Medika Ltd.	Sevlievo		Bulgaria	5400
110	UMHAT Aleksandrovska	Sofia		Bulgaria	1431
111	DCC "Sveta Anna"EOOD	Sofia		Bulgaria	1709
112	Aggarwal and Associates Limited	Brampton	Ontario	Canada	L6T 0G1
113	NRK Medical Research Clinic (Adminstrative Office Only)	London	Ontario	Canada	N6H 4P2
114	NRK Medical Research Clinic	London	Ontario	Canada	N6H 4P2
115	London Road Diagnostic Clinic and Medical Centre	Sarnia	Ontario	Canada	N7T 4X3
116	General Hospital "dr. Ivo Pedisic"	Sisak		Croatia	44000
117	Glostrup Hospital	Glostrup		Denmark	2600
118	Klinische Forschung Hannover-Mitte GmbH	Hannover	Niedersachsen	Germany	30159
119	Praxis für Spezielle Schmerztherapie und Palliativmedizin	Böhlen	Sachsen	Germany	04564
120	medamed GmbH Studienambulanz	Leipzig	Sachsen	Germany	04109
121	pro scientia med im MARE Klinikum	Kiel-Kronshagen	Schleswig-holstein	Germany	24119
122	Klinische Forschung Berlin-Mitte GmbH	Berlin		Germany	10117
123	Synexus Clinical Research GmbH	Berlin		Germany	12627
124	Synexus Clinical Research GmbH	Bochum		Germany	44787
125	Synexus Clinical Research GmbH	Frankfurt		Germany	60596
126	Klinische Forschung Hamburg GmbH	Hamburg		Germany	20253
127	Gemeinschaftspraxis für Schmerz- und Psychotherapie	Hamburg		Germany	22767
128	Synexus Clinical Research GmbH	Leipzig		Germany	04103
129	Klinische Forschung Schwerin GmbH	Schwerin		Germany	19055
130	Synexus Magyarorszag Kft.	Budapest		Hungary	1036
131	UNO Medical Trials Kft	Budapest		Hungary	1135
132	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc		Hungary	3526
133	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
134	Niepubliczny Zaklad Opieki Zdrowotnej "Przychodnia Morena" Sp. z.o.o.	Gdansk		Poland	80-286
135	"SYNEXUS POLSKA" Sp. z o.o. Oddzial w Gdyni	Gdynia		Poland	81-384
136	"Synexus Polska" Sp. z o.o. Oddzial W Katowicach	Katowice		Poland	40-040
137	Malopolskie Centrum Medyczne S.C.	Krakow		Poland	30-510
138	NZOZ IGNIS dr n. med. Alicja Lobinska	Swidnik		Poland	21-040
139	"SYNEXUS Polska" Sp. z o.o. ODDZIAL W WARSZAWIE	Warszawa		Poland	01-192
140	"SYNEXUS POLSKA" Sp. z o.o. Odzial we Wroclawiu	Wroclaw		Poland	50-088
141	Ponce School of Medicine, CAIMED Center	Ponce		Puerto Rico	00716
142	Centrul Medical Sana	Bucuresti		Romania	011025
143	Clubul Sanatatii SRL	Campulung Muscel		Romania	115100
144	Spitalul Clinic de Neuropsihiatrie Craiova	Craiova		Romania	200473
145	Spitalul Clinic Municipal Dr. Gavril Curteanu Oradea,Sectia Neurologie I	Oradea		Romania	410154
146	Spitalul Clinic Judetean de Urgenta Sibiu,Sectia Neurologie	Sibiu		Romania	550166
147	Spitalul Clinic Judetean de Urgenta Targu-Mures , Sectia Neurologie II	Targu Mures		Romania	540136
148	Welkom Clinical Trial Centre	Welkom	FREE State	South Africa	9460
149	Synexus SA - Stanza Clinical Research Centre	Pretoria	Gauteng	South Africa	0122
150	Synexus SA - Watermeyer Clinical Research Centre	Pretoria	Gauteng	South Africa	0184
151	Synexus SA - Roodepoort Medicross Clinical Research Centre	Roodeport	Gauteng	South Africa	1724
152	Ladulaas Kliniken	Boras		Sweden	506 30
153	CTC, Gothia Forum, Sahlgrenska Universitetssjukhus	Göteborg		Sweden	413 45
154	Probare	Lund		Sweden	222 22
155	Pharmasite	Malmö		Sweden	211 52
156	Bragee Medect AB	Stockholm		Sweden	115 26

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01701362
• Other Study ID Numbers: A0081279; 2012-003304-12
• First Posted: Oct 5, 2012
• Last Update Posted: Jan 28, 2021
• Last Verified: Apr 1, 2017

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: post-traumatic peripheral neuropathic pain
• Additional relevant MeSH terms: Neuralgia; Pregabalin

Study Results

Participant Flow

Recruitment Details	A total of 187 centers participated in the study in 14 countries. During screening, with the exception of daily pain score data that was collected to determine participants eligibility, no participants were treated with active drug and no efficacy data were collected. Only safety and no efficacy data was collected during the taper period.
Pre-assignment Detail	Participants had clinic visits at screening, randomization, and during the treatment period, and a phone contact for follow-up after the last taper dose. All the eligible participants were randomly assigned (1:1) to 15 weeks of treatment with Pregabalin or Placebo.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Period Title: Overall Study
STARTED	275	267
TREATED	274	265
COMPLETED	233	211
NOT COMPLETED	42	56

Baseline Characteristics

Arm/Group Title	Pregabalin	Placebo	Total
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo	Total of all reporting groups
Overall Participants	274	265	539
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.8 (12.9)	53.4 (12.7)	53.1 (12.8)
Age, Customized (Number) [Number]
18 - 44 years	59 21.5%	61 23%	120 22.3%
45 - 64 years	163 59.5%	154 58.1%	317 58.8%
>=65 years	52 19%	50 18.9%	102 18.9%
Sex: Female, Male (Count of Participants)
Female	132 48.2%	134 50.6%	266 49.4%
Male	142 51.8%	131 49.4%	273 50.6%

Outcome Measures

1. Primary Outcome

Title	Baseline Mean Pain Score
Description	This is based on the daily pain dairy and is defined as the baseline mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Mean (Standard Deviation) [units on a scale]	6.41 (1.30)	6.54 (1.30)

2. Primary Outcome

Title	Change From Baseline to Week 15 in Weekly Mean Pain Score
Description	This is based on the daily pain diary and is defined as the change from baseline to week 15 in mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10.
Time Frame	up to Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Least Squares Mean (Standard Error) [units on a scale]	-2.12 (0.15)	-1.90 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1823
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Mixed Model Repeated Measures = MMRM
Method of Estimation	Estimation Parameter	least squares mean difference
	Estimated Value	-0.22
	Confidence Interval	() 95%; -0.54 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments	MMRM analysis includes fixed categorical effects of treatment, country, trauma type, visit week, treatment-by-visit interaction, and fixed continuous effect of baseline value. Missing mean pain scores imputed by multiple imputation method

3. Secondary Outcome

Title	Patient Global Impression of Change (PGIC) at Week 15
Description	A self administered instrument that measures changes in participants' overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). The PGIC is based on the Clinical Global Impression of Change, which is a validated scale.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	258	246
Very much improved	52 19%	41 15.5%
Much improved	105 38.3%	79 29.8%
Minimally improved	61 22.3%	62 23.4%
No change	34 12.4%	51 19.2%
Minimally worse	5 1.8%	9 3.4%
Much worse	0 0%	4 1.5%
Very much worse	1 0.4%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	The p-value is derived from CMH test, stratified for pooled center and trauma type and excludes missing values.
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Description	This is an 11-point NRS ranging from 0 ("pain does not interfere with sleep") to 10 ("pain completely interferes with sleep" [unable to sleep due to pain]). Participants describe how pain has interfered with their sleep during the past 24 hours. Please note that the data for Baseline (raw scores) have been included in the below table to read the change from Baseline data in context. Note: Weekly mean SIRS scores were derived from the daily sleep diary and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean SIRS scores were defined as the mean of the 7 daily diary SIRS scores from Day 2+7 (n-1) to Day 1+7*n. For participants with multiple diary scores collected on the same day, the average of all non-missing scores for that day was used in any analyses or data listings. "Overall" is the pooled average sleep interference score for each subject across all post-baseline/randomization weeks.
Time Frame	up to Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Baseline (raw scores) (N = 274, 265)	4.97 (2.30)	4.99 (2.27)
Week 1 (N = 260, 258)	-0.66 (1.10)	-0.28 (0.91)
Week 2 (N = 254, 244)	-1.15 (1.51)	-0.81 (1.27)
Week 3 (N = 252, 245)	-1.55 (1.73)	-1.14 (1.45)
Week 4 (N = 245, 229)	-1.73 (1.80)	-1.30 (1.63)
Week 5 (N = 241, 226)	-1.87 (1.87)	-1.40 (1.68)
Week 6 (N = 244, 227)	-1.94 (1.95)	-1.46 (1.79)
Week 7 (N = 240, 216)	-2.01 (1.99)	-1.50 (1.78)
Week 8 (N = 236, 212)	-2.05 (2.00)	-1.52 (1.76)
Week 9 (N = 232, 214)	-2.09 (1.99)	-1.55 (1.86)
Week 10 (N = 229, 212)	-2.04 (2.11)	-1.55 (1.83)
Week 11 (N = 230, 211)	-2.09 (2.05)	-1.64 (1.79)
Week 12 (N = 227, 209)	-2.17 (2.06)	-1.68 (1.89)
Week 13 (N = 225, 204)	-2.19 (2.06)	-1.70 (1.90)
Week 14 (N = 222, 208)	-2.19 (2.16)	-1.79 (1.89)
Week 15 (N = 196, 186)	-2.13 (2.17)	-1.83 (1.87)
Overall (N = 269, 262)	-1.83 (1.93)	-1.37 (1.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0119
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.35
	Confidence Interval	() 95%; -0.62 to -0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0135
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.34
	Confidence Interval	() 95%; -0.62 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.42
	Confidence Interval	() 95%; -0.69 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.44
	Confidence Interval	() 95%; -0.72 to -0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.48
	Confidence Interval	() 95%; -0.75 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.48
	Confidence Interval	() 95%; -0.76 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 7
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.48
	Confidence Interval	() 95%; -0.75 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 8
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.52
	Confidence Interval	() 95%; -0.79 to -0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 9
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.54
	Confidence Interval	() 95%; -0.82 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 10
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.49
	Confidence Interval	() 95%; -0.77 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 11
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.48
	Confidence Interval	() 95%; -0.76 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 12
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.54
	Confidence Interval	() 95%; -0.82 to -0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 13
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.56
	Confidence Interval	() 95%; -0.84 to -0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 14
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.50
	Confidence Interval	() 95%; -0.78 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Week 15
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.43
	Confidence Interval	() 95%; -0.71 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Overall
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Model Repeated Measures Analysis
	Comments	Analyzed for treatment, center, trauma type, week & treatment-by-week interaction and fixed continuous effect of baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.47
	Confidence Interval	() 95%; -0.71 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Pain Severity Index (Brief Pain Inventory-short Form [BPI-sf])
Description	A self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. The BPI-sf consists of 5 questions. Four items measure pain on 11-point response scales from 0 (No Pain) to 10 (Pain as bad as you can imagine). In the above scale, score 0 indicates the better outcome whereas score 10 indicates the worse outcome.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	258	246
Least Squares Mean (Standard Error) [units on a scale]	-2.40 (0.13)	-1.95 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments
	Method	ANCOVA
	Comments	This secondary endpoint has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least squares mean difference
	Estimated Value	-0.46
	Confidence Interval	() 95%; -0.77 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Pain Interference Index (BPI-sf)
Description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. It consists of 7 sub-questions that evaluates the level of pain interference with daily functioning on 11-point response scales from 0 (does not interfere) to 10 (completely interferes). The BPI-sf pain interference index was calculated as average of the seven individual pain interference scores.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Least Squares Mean (Standard Error) [units on a scale]	-1.72 (0.13)	-1.33 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0168
	Comments
	Method	ANCOVA
	Comments	This secondary endpoint has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	() 95%; -0.70 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Description	A self-administered questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression. Each dimension is rated on a 3 point response scale and the scores are combined to form a single index value between 0 and 1 with higher scores being more positive (better health status). The EQ-5D was completed by the subject at week-0 and week-15/ET where 30% responder and 50% responder status would be defined for each participants based on the percent change from baseline (week 0/Randomization) to each visit week in mean pain score and participant global impression of change (PGIC). PGIC is a self-administered instrument that measures change in participant's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). It is based on the Clinical Global Impression of Change CGIC), which is a validated scale.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Mobility	-0.10 (0.03)	-0.09 (0.03)
Self-care	-0.08 (0.02)	-0.06 (0.02)
Usual activities	-0.12 (0.03)	-0.13 (0.04)
Pain/Discomfort	-0.35 (0.03)	-0.29 (0.04)
Anxiety/Depression	0.01 (0.03)	-0.02 (0.03)
Dolan 1997 Index Score	0.12 (0.01)	0.11 (0.01)
Dolan 2001 Index Score	-0.13 (0.02)	-0.12 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This statistical analysis is for mobility
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6841
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least squares mean difference
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.09 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This statistical analysis is for self-care
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6564
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least squares mean difference
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.07 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.029
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This statistical analysis is for usual activities
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8590
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least squares mean difference
	Estimated Value	0.01
	Confidence Interval	() 95%; -0.08 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.043
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This statistical analysis is for pain/discomfort
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1628
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least squares mean difference
	Estimated Value	-0.06
	Confidence Interval	() 95%; -0.14 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.043
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This statistical analysis is for anxiety/depression
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4654
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	leaset squares mean difference
	Estimated Value	0.03
	Confidence Interval	() 95%; -0.05 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This statistical analysis is for Dolan 1997 Index score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5000
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least squares mean difference
	Estimated Value	0.01
	Confidence Interval	() 95%; -0.02 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.017
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This statistical analysis is for Dolan 2001 Index Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5493
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	leaset squares mean difference
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.07 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.026
	Estimation Comments

8. Secondary Outcome

Title	Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Description	MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Sleep Disturbance Score (N = 274, 265)	42.50 (25.791)	43.75 (25.080)
Sleep Adequancy Score (N = 274, 265)	40.0 (28.153)	40.0 (28.582)
Snoring Score (N = 272, 263)	20.0 (33.482)	20.0 (34.084)
Awaken Short of Breath Score (N = 274, 265)	0.0 (25.647)	0.0 (21.541)
Quantity of Sleep Score (hours) (N = 273, 265)	6.0 (1.360)	6.0 (1.411)
Somnolence Score (N = 274, 265)	26.67 (21.618)	26.67 (19.884)
Sleep Problem Index (9) Score (N = 274, 265)	40.56 (20.282)	41.11 (19.720)
Optimal Sleep Score (N = 273, 265)	0.0 (0.476)	0.0 (0.487)

9. Secondary Outcome

Title	Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Description	MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Sleep Disturbance Score (N = 257, 245)	-14.71	-11.24
Sleep Adequancy Score (N=257, 245)	10.13	8.16
Snoring Score (N = 257, 245)	-2.22	-3.27
Awaken Short of Breath Score (N = 257, 245)	-3.61	-3.03
Quantity of Sleep Score (hours) (N = 257, 245)	0.42	0.26
Somnolence Score (N = 257, 245)	-1.61	-3.74
Sleep Problem Index (9) Score (N = 257, 245)	-9.86	-8.19
Optimal Sleep Score (N = 256, 245)	0.11	0.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis for Sleep Disturbance Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0545
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	3.5
	Confidence Interval	() 95%; -0.07 to 7.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.80
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis for Sleep Adequancy Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3913
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-2.0
	Confidence Interval	() 95%; -6.47 to 2.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.29
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis for Snoring Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6059
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-1.1
	Confidence Interval	() 95%; -5.06 to 2.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.04
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis for Awaken Short of Breath Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7317
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	0.6
	Confidence Interval	() 95%; -2.76 to 3.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.70
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis for Quantity of Sleep Score (hours)
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2663
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-0.2
	Confidence Interval	() 95%; -0.45 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin
	Comments	Statistical analysis for Somnolence Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1562
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	-2.1
	Confidence Interval	() 95%; -5.08 to 0.82
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.50
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis for Sleep Problem Index (9) Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2490
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	least square mean difference
	Estimated Value	1.7
	Confidence Interval	() 95%; -1.18 to 4.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.45
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis for Optimal Sleep Score
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0609
	Comments
	Method	ANCOVA
	Comments	This sub-score has been analyzed using ANCOVA with model terms of treatment, center, trauma type and baseline value on the ITT population.
Method of Estimation	Estimation Parameter	leaet squares mean difference
	Estimated Value	-0.1
	Confidence Interval	() 95%; -0.15 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants in MOS-SS With Optimal Sleep Status.
Description	MOS-SS optimal sleep status analyzed on a scale of four parameters: any improvements, no change, any worsening and not applicable.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized subjects who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Any Improvements	21.2 7.7%	18.5 7%
No Change	66.1 24.1%	60.8 22.9%
Any Worsening	6.2 2.3%	13.2 5%
Not applicable	6.6 2.4%	7.5 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7165
	Comments	p-values based on CMH test stratified by pooled center and trauma type, patients with unknown status at baseline or endpoint will not be included in the calculation of p-values.
	Method	Cochran-Mantel-Haenszel
	Comments

11. Secondary Outcome

Title	Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Description	Participants with at least 30% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Week 1 (N = 260, 258)	11.92 4.4%	5.04 1.9%
Week 2 (N = 254, 244)	27.17 9.9%	20.08 7.6%
Week 3 (N = 252, 245)	38.89 14.2%	30.20 11.4%
Week 4 (N = 246, 229)	41.87 15.3%	34.50 13%
Week 5 (N = 241, 226)	45.64 16.7%	38.05 14.4%
Week 6 (N = 244, 227)	48.77 17.8%	41.41 15.6%
Week 7 (N = 240, 216)	49.58 18.1%	43.06 16.2%
Week 8 (N = 236, 213)	50.42 18.4%	46.48 17.5%
Week 9 (N = 232, 214)	50.86 18.6%	47.66 18%
Week 10 (N = 229, 212)	52.84 19.3%	47.17 17.8%
Week 11 (N = 231, 211)	52.38 19.1%	51.18 19.3%
Week 12 (N = 227, 209)	54.63 19.9%	52.63 19.9%
Week 13 (N = 226, 204)	57.08 20.8%	54.41 20.5%
Week 14 (N = 223, 208)	57.40 20.9%	54.33 20.5%
Week 15 (N = 196, 187)	57.65 21%	58.29 22%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.20
	Confidence Interval	() 95%; 1.50 to 6.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0360
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.66
	Confidence Interval	() 95%; 1.03 to 2.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0235
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.62
	Confidence Interval	() 95%; 1.07 to 2.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0619
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.48
	Confidence Interval	() 95%; 0.98 to 2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0677
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.46
	Confidence Interval	() 95%; 0.97 to 2.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0707
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	() 95%; 0.97 to 2.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 7
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1313
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.37
	Confidence Interval	() 95%; 0.91 to 2.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 8
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3072
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.24
	Confidence Interval	() 95%; 0.82 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 9
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3947
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	() 95%; 0.79 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 10
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1462
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	() 95%; 0.90 to 2.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 11
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6854
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.09
	Confidence Interval	() 95%; 0.72 to 1.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 12
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5025
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	() 95%; 0.76 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 13
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4908
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	() 95%; 0.76 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 14
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4245
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	() 95%; 0.78 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 15
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8464
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	() 95%; 0.61 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Description	Participants with at least 50% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain.
Time Frame	Week 15

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who took at least one dose of study drug

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.	Participants randomized to receive placebo
Measure Participants	274	265
Week 1 (N = 260, 258)	4.62 1.7%	2.33 0.9%
Week 2 (N = 254, 244)	11.42 4.2%	6.97 2.6%
Week 3 (N = 252, 245)	22.62 8.3%	13.47 5.1%
Week 4 (N = 246, 229)	25.20 9.2%	17.90 6.8%
Week 5 (N = 241, 226)	28.22 10.3%	19.47 7.3%
Week 6 (N = 244, 227)	29.51 10.8%	22.91 8.6%
Week 7 (N= 240, 216)	30.42 11.1%	22.22 8.4%
Week 8 (N = 236, 213)	33.05 12.1%	27.70 10.5%
Week 9 (N = 232, 214)	34.05 12.4%	26.17 9.9%
Week 10 (N = 229, 212)	32.75 12%	26.42 10%
Week 11 (N = 231, 211)	34.20 12.5%	25.59 9.7%
Week 12 (N = 227, 209)	37.89 13.8%	26.79 10.1%
Week 13 (N = 226, 204)	35.84 13.1%	27.45 10.4%
Week 14 (N = 223, 208)	37.67 13.7%	29.81 11.2%
Week 15 (N = 196, 187)	39.80 14.5%	34.22 12.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 1
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1633
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.11
	Confidence Interval	() 95%; 0.74 to 6.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 2
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0652
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.92
	Confidence Interval	() 95%; 0.96 to 3.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 3
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.20
	Confidence Interval	() 95%; 1.29 to 3.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 4
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0382
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	() 95%; 1.03 to 2.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 5
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.86
	Confidence Interval	() 95%; 1.14 to 3.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 6
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0693
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	() 95%; 0.97 to 2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 7
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0349
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.68
	Confidence Interval	() 95%; 1.04 to 2.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 8
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1227
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	() 95%; 0.91 to 2.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 9
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0364
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.65
	Confidence Interval	() 95%; 1.03 to 2.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 10
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0667
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	() 95%; 0.97 to 2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 11
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0176
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.77
	Confidence Interval	() 95%; 1.10 to 2.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 12
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0030
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.03
	Confidence Interval	() 95%; 1.27 to 3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 13
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0256
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	() 95%; 1.07 to 2.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 14
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0314
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.66
	Confidence Interval	() 95%; 1.05 to 2.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis at Week 15
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1889
	Comments
	Method	Gen linear model-logistic link function
	Comments	Model terms include categorical: treatment, center, trauma type, week, and treatment-by-week interaction; and continuous: baselines mean pain score.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.38
	Confidence Interval	() 95%; 0.85 to 2.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
Adverse Event Reporting Description	The adverse events reporting period was from the signing of the informed consent (at screening) throughout the study including 28 calendar days from the last dose of study medication.
Arm/Group Title	Pregabalin		Placebo
Arm/Group Description	Participants randomized to receive pregabalin: a 3-week dose optimization phase followed by 150 mg, 300 mg, 450 mg or 600 mg per day dosing 12-week maintenance phase.		Participants randomized to receive placebo
All Cause Mortality
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/274 (0.7%)		7/265 (2.6%)
Cardiac disorders
Atrial fibrillation	1/274 (0.4%)	1	0/265 (0%)	0
Gastrointestinal disorders
Haemorrhoids	0/274 (0%)	0	1/265 (0.4%)	1
Infections and infestations
Urinary tract infection	1/274 (0.4%)	1	0/265 (0%)	0
Injury, poisoning and procedural complications
Concussion	0/274 (0%)	0	1/265 (0.4%)	1
Overdose	0/274 (0%)	0	1/265 (0.4%)	1
Post procedural discharge	0/274 (0%)	0	1/265 (0.4%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/274 (0.4%)	2	0/265 (0%)	0
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	0/274 (0%)	0	1/265 (0.4%)	1
Nervous system disorders
Headache	1/274 (0.4%)	1	0/265 (0%)	0
Hypoglycaemic seizure	1/274 (0.4%)	1	0/265 (0%)	0
Psychiatric disorders
Major depression	0/274 (0%)	0	1/265 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/274 (0%)	0	1/265 (0.4%)	1
Pneumonia aspiration	0/274 (0%)	0	1/265 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/274 (27.4%)		33/265 (12.5%)
Gastrointestinal disorders
Nausea	14/274 (5.1%)	15	8/265 (3%)	8
General disorders
Fatigue	14/274 (5.1%)	16	10/265 (3.8%)	10
Nervous system disorders
Dizziness	40/274 (14.6%)	51	11/265 (4.2%)	13
Somnolence	27/274 (9.9%)	31	9/265 (3.4%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.