Trial Outcomes & Findings for Placebo-controlled Safety and Efficacy Study of Pregabalin in Subjects With Post-traumatic Peripheral Neuropathic Pain (NCT NCT01701362)
NCT ID: NCT01701362
Last Updated: 2021-01-28
Results Overview
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.
COMPLETED
PHASE3
542 participants
Baseline
2021-01-28
Participant Flow
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.
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.
Participant milestones
| Measure |
Pregabalin
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.
|
Placebo
Participants randomized to receive placebo
|
|---|---|---|
|
Overall Study
STARTED
|
275
|
267
|
|
Overall Study
TREATED
|
274
|
265
|
|
Overall Study
COMPLETED
|
233
|
211
|
|
Overall Study
NOT COMPLETED
|
42
|
56
|
Reasons for withdrawal
| Measure |
Pregabalin
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.
|
Placebo
Participants randomized to receive placebo
|
|---|---|---|
|
Overall Study
Adverse events not related to study drug
|
1
|
6
|
|
Overall Study
Adverse events related to study drug
|
12
|
10
|
|
Overall Study
Protocol Violation
|
5
|
3
|
|
Overall Study
No longer willing to participate
|
8
|
14
|
|
Overall Study
Lost to Follow-up
|
6
|
9
|
|
Overall Study
Insufficient clinical response
|
6
|
6
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Randomized but not treated
|
1
|
2
|
|
Overall Study
Reasons other than those mentioned above
|
3
|
5
|
Baseline Characteristics
Placebo-controlled Safety and Efficacy Study of Pregabalin in Subjects With Post-traumatic Peripheral Neuropathic Pain
Baseline characteristics by cohort
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
Total
n=539 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.8 Years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
53.4 Years
STANDARD_DEVIATION 12.7 • n=7 Participants
|
53.1 Years
STANDARD_DEVIATION 12.8 • n=5 Participants
|
|
Age, Customized
18 - 44 years
|
59 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Age, Customized
45 - 64 years
|
163 Participants
n=5 Participants
|
154 Participants
n=7 Participants
|
317 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
52 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
102 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
132 Participants
n=5 Participants
|
134 Participants
n=7 Participants
|
266 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
142 Participants
n=5 Participants
|
131 Participants
n=7 Participants
|
273 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: BaselinePopulation: Intent to Treat (ITT) population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Baseline Mean Pain Score
|
6.41 units on a scale
Standard Deviation 1.30
|
6.54 units on a scale
Standard Deviation 1.30
|
PRIMARY outcome
Timeframe: up to Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Change From Baseline to Week 15 in Weekly Mean Pain Score
|
-2.12 units on a scale
Standard Error 0.15
|
-1.90 units on a scale
Standard Error 0.16
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=258 Participants
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.
|
Placebo
n=246 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Patient Global Impression of Change (PGIC) at Week 15
Minimally improved
|
61 Participants
|
62 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 15
Much worse
|
0 Participants
|
4 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 15
Very much improved
|
52 Participants
|
41 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 15
Much improved
|
105 Participants
|
79 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 15
No change
|
34 Participants
|
51 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 15
Minimally worse
|
5 Participants
|
9 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 15
Very much worse
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: up to Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 1 (N = 260, 258)
|
-0.66 units on a scale
Standard Deviation 1.10
|
-0.28 units on a scale
Standard Deviation 0.91
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 3 (N = 252, 245)
|
-1.55 units on a scale
Standard Deviation 1.73
|
-1.14 units on a scale
Standard Deviation 1.45
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 4 (N = 245, 229)
|
-1.73 units on a scale
Standard Deviation 1.80
|
-1.30 units on a scale
Standard Deviation 1.63
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 9 (N = 232, 214)
|
-2.09 units on a scale
Standard Deviation 1.99
|
-1.55 units on a scale
Standard Deviation 1.86
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 10 (N = 229, 212)
|
-2.04 units on a scale
Standard Deviation 2.11
|
-1.55 units on a scale
Standard Deviation 1.83
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 11 (N = 230, 211)
|
-2.09 units on a scale
Standard Deviation 2.05
|
-1.64 units on a scale
Standard Deviation 1.79
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 13 (N = 225, 204)
|
-2.19 units on a scale
Standard Deviation 2.06
|
-1.70 units on a scale
Standard Deviation 1.90
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 14 (N = 222, 208)
|
-2.19 units on a scale
Standard Deviation 2.16
|
-1.79 units on a scale
Standard Deviation 1.89
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Baseline (raw scores) (N = 274, 265)
|
4.97 units on a scale
Standard Deviation 2.30
|
4.99 units on a scale
Standard Deviation 2.27
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 2 (N = 254, 244)
|
-1.15 units on a scale
Standard Deviation 1.51
|
-0.81 units on a scale
Standard Deviation 1.27
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 5 (N = 241, 226)
|
-1.87 units on a scale
Standard Deviation 1.87
|
-1.40 units on a scale
Standard Deviation 1.68
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 6 (N = 244, 227)
|
-1.94 units on a scale
Standard Deviation 1.95
|
-1.46 units on a scale
Standard Deviation 1.79
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 7 (N = 240, 216)
|
-2.01 units on a scale
Standard Deviation 1.99
|
-1.50 units on a scale
Standard Deviation 1.78
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 8 (N = 236, 212)
|
-2.05 units on a scale
Standard Deviation 2.00
|
-1.52 units on a scale
Standard Deviation 1.76
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 12 (N = 227, 209)
|
-2.17 units on a scale
Standard Deviation 2.06
|
-1.68 units on a scale
Standard Deviation 1.89
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Week 15 (N = 196, 186)
|
-2.13 units on a scale
Standard Deviation 2.17
|
-1.83 units on a scale
Standard Deviation 1.87
|
|
Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)
Overall (N = 269, 262)
|
-1.83 units on a scale
Standard Deviation 1.93
|
-1.37 units on a scale
Standard Deviation 1.71
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=258 Participants
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.
|
Placebo
n=246 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Change From Baseline in Pain Severity Index (Brief Pain Inventory-short Form [BPI-sf])
|
-2.40 units on a scale
Standard Error 0.13 • Interval -8.3 to 2.5
|
-1.95 units on a scale
Standard Error 0.13 • Interval -6.5 to 2.5
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Change From Baseline in Pain Interference Index (BPI-sf)
|
-1.72 units on a scale
Standard Error 0.13 • Interval -1.97 to -1.46
|
-1.33 units on a scale
Standard Error 0.13 • Interval -1.59 to -1.07
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Self-care
|
-0.08 Units on a scale
Standard Error 0.02 • Interval -0.12 to 0.04
|
-0.06 Units on a scale
Standard Error 0.02 • Interval -0.11 to -0.02
|
|
Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Mobility
|
-0.10 Units on a scale
Standard Error 0.03 • Interval -0.16 to -0.05
|
-0.09 Units on a scale
Standard Error 0.03 • Interval -0.15 to -0.03
|
|
Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Usual activities
|
-0.12 Units on a scale
Standard Error 0.03 • Interval -0.19 to -0.05
|
-0.13 Units on a scale
Standard Error 0.04 • Interval -0.2 to -0.06
|
|
Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Pain/Discomfort
|
-0.35 Units on a scale
Standard Error 0.03 • Interval -0.42 to -0.28
|
-0.29 Units on a scale
Standard Error 0.04 • Interval -0.36 to -0.22
|
|
Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Anxiety/Depression
|
0.01 Units on a scale
Standard Error 0.03 • Interval -0.05 to 0.07
|
-0.02 Units on a scale
Standard Error 0.03 • Interval -0.08 to 0.04
|
|
Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Dolan 1997 Index Score
|
0.12 Units on a scale
Standard Error 0.01
|
0.11 Units on a scale
Standard Error 0.01
|
|
Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores
Dolan 2001 Index Score
|
-0.13 Units on a scale
Standard Error 0.02
|
-0.12 Units on a scale
Standard Error 0.02
|
SECONDARY outcome
Timeframe: BaselinePopulation: ITT population: all randomized participants who took at least one dose of study drug.
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Sleep Adequancy Score (N = 274, 265)
|
40.0 Units on a scale
Full Range 28.153 • Interval 0.0 to 100.0
|
40.0 Units on a scale
Full Range 28.582 • Interval 0.0 to 100.0
|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Quantity of Sleep Score (hours) (N = 273, 265)
|
6.0 Units on a scale
Full Range 1.360 • Interval 2.0 to 10.0
|
6.0 Units on a scale
Full Range 1.411 • Interval 2.0 to 10.0
|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Somnolence Score (N = 274, 265)
|
26.67 Units on a scale
Full Range 21.618 • Interval 0.0 to 100.0
|
26.67 Units on a scale
Full Range 19.884 • Interval 0.0 to 100.0
|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Sleep Problem Index (9) Score (N = 274, 265)
|
40.56 Units on a scale
Full Range 20.282 • Interval 0.0 to 88.3
|
41.11 Units on a scale
Full Range 19.720 • Interval 0.0 to 88.9
|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Optimal Sleep Score (N = 273, 265)
|
0.0 Units on a scale
Full Range 0.476 • Interval 0.0 to 1.0
|
0.0 Units on a scale
Full Range 0.487 • Interval 0.0 to 1.0
|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Sleep Disturbance Score (N = 274, 265)
|
42.50 Units on a scale
Full Range 25.791 • Interval 0.0 to 100.0
|
43.75 Units on a scale
Full Range 25.080 • Interval 0.0 to 100.0
|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Snoring Score (N = 272, 263)
|
20.0 Units on a scale
Full Range 33.482 • Interval 0.0 to 100.0
|
20.0 Units on a scale
Full Range 34.084 • Interval 0.0 to 100.0
|
|
Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Awaken Short of Breath Score (N = 274, 265)
|
0.0 Units on a scale
Full Range 25.647 • Interval 0.0 to 100.0
|
0.0 Units on a scale
Full Range 21.541 • Interval 0.0 to 100.0
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized participants who took at least one dose of study drug.
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Sleep Disturbance Score (N = 257, 245)
|
-14.71 Units on a scale
Interval -17.57 to -11.85
|
-11.24 Units on a scale
Interval -14.16 to -8.33
|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Somnolence Score (N = 257, 245)
|
-1.61 Units on a scale
Interval -3.99 to 0.77
|
-3.74 Units on a scale
Interval -6.17 to -1.31
|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Sleep Adequancy Score (N=257, 245)
|
10.13 Units on a scale
Interval 6.49 to 13.76
|
8.16 Units on a scale
Interval 4.43 to 11.89
|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Snoring Score (N = 257, 245)
|
-2.22 Units on a scale
Interval -5.46 to 1.03
|
-3.27 Units on a scale
Interval -6.59 to 0.04
|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Awaken Short of Breath Score (N = 257, 245)
|
-3.61 Units on a scale
Interval -6.3 to -0.92
|
-3.03 Units on a scale
Interval -5.78 to -0.27
|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Quantity of Sleep Score (hours) (N = 257, 245)
|
0.42 Units on a scale
Interval 0.19 to 0.66
|
0.26 Units on a scale
Interval 0.03 to 0.5
|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Sleep Problem Index (9) Score (N = 257, 245)
|
-9.86 Units on a scale
Interval -12.17 to -7.56
|
-8.19 Units on a scale
Interval -10.55 to -5.83
|
|
Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.
Optimal Sleep Score (N = 256, 245)
|
0.11 Units on a scale
Interval 0.05 to 0.18
|
0.04 Units on a scale
Interval -0.03 to 0.1
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized subjects who took at least one dose of study drug
MOS-SS optimal sleep status analyzed on a scale of four parameters: any improvements, no change, any worsening and not applicable.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Percentage of Participants in MOS-SS With Optimal Sleep Status.
Any Improvements
|
21.2 Percentage of participants
|
18.5 Percentage of participants
|
|
Percentage of Participants in MOS-SS With Optimal Sleep Status.
No Change
|
66.1 Percentage of participants
|
60.8 Percentage of participants
|
|
Percentage of Participants in MOS-SS With Optimal Sleep Status.
Any Worsening
|
6.2 Percentage of participants
|
13.2 Percentage of participants
|
|
Percentage of Participants in MOS-SS With Optimal Sleep Status.
Not applicable
|
6.6 Percentage of participants
|
7.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 1 (N = 260, 258)
|
11.92 Percentage of participants
|
5.04 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 2 (N = 254, 244)
|
27.17 Percentage of participants
|
20.08 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 5 (N = 241, 226)
|
45.64 Percentage of participants
|
38.05 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 7 (N = 240, 216)
|
49.58 Percentage of participants
|
43.06 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 11 (N = 231, 211)
|
52.38 Percentage of participants
|
51.18 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 13 (N = 226, 204)
|
57.08 Percentage of participants
|
54.41 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 14 (N = 223, 208)
|
57.40 Percentage of participants
|
54.33 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 3 (N = 252, 245)
|
38.89 Percentage of participants
|
30.20 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 4 (N = 246, 229)
|
41.87 Percentage of participants
|
34.50 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 6 (N = 244, 227)
|
48.77 Percentage of participants
|
41.41 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 8 (N = 236, 213)
|
50.42 Percentage of participants
|
46.48 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 9 (N = 232, 214)
|
50.86 Percentage of participants
|
47.66 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 10 (N = 229, 212)
|
52.84 Percentage of participants
|
47.17 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 12 (N = 227, 209)
|
54.63 Percentage of participants
|
52.63 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%.
Week 15 (N = 196, 187)
|
57.65 Percentage of participants
|
58.29 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 15Population: ITT population: all randomized participants who took at least one dose of study drug
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.
Outcome measures
| Measure |
Pregabalin
n=274 Participants
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.
|
Placebo
n=265 Participants
Participants randomized to receive placebo
|
|---|---|---|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 5 (N = 241, 226)
|
28.22 Percentage of participants
|
19.47 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 14 (N = 223, 208)
|
37.67 Percentage of participants
|
29.81 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 1 (N = 260, 258)
|
4.62 Percentage of participants
|
2.33 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 2 (N = 254, 244)
|
11.42 Percentage of participants
|
6.97 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 3 (N = 252, 245)
|
22.62 Percentage of participants
|
13.47 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 4 (N = 246, 229)
|
25.20 Percentage of participants
|
17.90 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 6 (N = 244, 227)
|
29.51 Percentage of participants
|
22.91 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 7 (N= 240, 216)
|
30.42 Percentage of participants
|
22.22 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 8 (N = 236, 213)
|
33.05 Percentage of participants
|
27.70 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 9 (N = 232, 214)
|
34.05 Percentage of participants
|
26.17 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 10 (N = 229, 212)
|
32.75 Percentage of participants
|
26.42 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 11 (N = 231, 211)
|
34.20 Percentage of participants
|
25.59 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 12 (N = 227, 209)
|
37.89 Percentage of participants
|
26.79 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 13 (N = 226, 204)
|
35.84 Percentage of participants
|
27.45 Percentage of participants
|
|
Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50%
Week 15 (N = 196, 187)
|
39.80 Percentage of participants
|
34.22 Percentage of participants
|
Adverse Events
Pregabalin
Placebo
Serious adverse events
| Measure |
Pregabalin
n=274 participants at risk
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.
|
Placebo
n=265 participants at risk
Participants randomized to receive placebo
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.36%
1/274 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.00%
0/265 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Infections and infestations
Urinary tract infection
|
0.36%
1/274 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.00%
0/265 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Injury, poisoning and procedural complications
Post procedural discharge
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.36%
1/274 • Number of events 2 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.00%
0/265 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Nervous system disorders
Headache
|
0.36%
1/274 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.00%
0/265 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Nervous system disorders
Hypoglycaemic seizure
|
0.36%
1/274 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.00%
0/265 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Psychiatric disorders
Major depression
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/274 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
0.38%
1/265 • Number of events 1 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
Other adverse events
| Measure |
Pregabalin
n=274 participants at risk
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.
|
Placebo
n=265 participants at risk
Participants randomized to receive placebo
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.1%
14/274 • Number of events 15 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
3.0%
8/265 • Number of events 8 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
General disorders
Fatigue
|
5.1%
14/274 • Number of events 16 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
3.8%
10/265 • Number of events 10 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Nervous system disorders
Dizziness
|
14.6%
40/274 • Number of events 51 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
4.2%
11/265 • Number of events 13 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
|
Nervous system disorders
Somnolence
|
9.9%
27/274 • Number of events 31 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
3.4%
9/265 • Number of events 10 • From Day -21 to Day 112 (week 16) i.e. from baseline until 1 day post last taper dose.
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER