Trial Outcomes & Findings for Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER). (NCT NCT00288639)

NCT ID: NCT00288639

Last Updated: 2021-01-22

Results Overview

Percentage change from baseline=\[(12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate)/ 8 week baseline period seizure frequency rate\] x 100. Seizure frequencies per 28-day period: = (total # of partial seizures in period x 28 / (total # of days in period).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 98 participants
• Primary outcome timeframe: 8 week baseline period & 12 week treatment observation period
• Results posted on: 2021-01-22

Participant Flow

Planned to enroll approximately 100 subjects with partial seizures at up to 10 study centers in Greece.

Single arm open label study without randomization. The study included the following 3 main phases with a total study treatment duration of up to 21 weeks: Treatment dose-optimization phase = 9 weeks. Treatment observation phase = 12 weeks.

Participant milestones

Measure	Pregabalin Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Overall Study STARTED	98
Overall Study COMPLETED	86
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Measure	Pregabalin Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Overall Study Adverse Event	5
Overall Study Lack of Efficacy	4
Overall Study Withdrawal by Subject	2
Overall Study Other	1

Baseline Characteristics

Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).

Baseline characteristics by cohort

Measure	Pregabalin n=98 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Age, Customized 18 to 44 years	69 Participants n=5 Participants
Age, Customized 45 to 64 years	25 Participants n=5 Participants
Age, Customized >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 week baseline period & 12 week treatment observation period

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Percentage change from baseline=[(12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate)/ 8 week baseline period seizure frequency rate] x 100. Seizure frequencies per 28-day period: = (total # of partial seizures in period x 28 / (total # of days in period).

Outcome measures

Measure

Pregabalin n=92 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period

-33.33 percentage change in events Interval -100.0 to 7566.67

SECONDARY outcome

Timeframe: 8 week baseline period and 21 week treatment period

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Percentage change from baseline = ((21 weeks-8 weeks)/8 weeks)*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.

Outcome measures

Measure

Pregabalin n=92 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).

Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the Whole 21 Week Open-label Treatment Period.

-29.39 percentage change in events Interval -100.0 to 7478.95

SECONDARY outcome

Timeframe: 8 week baseline period and 21 week treatment period

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure date from patients who discontinued during any of these 4 week intervals will not be included in the summary for that interval.

Percentage change from baseline = [(4 week seizure frequency minus 8 week baseline) / (8 week baseline seizure frequency)] x 100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.

Outcome measures

Measure	Pregabalin n=92 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. 1-28 Days	-28.12 percentage change of events Interval -100.0 to 4833.33
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. 29-56 Days	-22.50 percentage change of events Interval -100.0 to 9633.33
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. 57-84 Days	-25.00 percentage change of events Interval -100.0 to 3433.33
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. 85-112 Days	-40.00 percentage change of events Interval -100.0 to 5100.0
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. 113-140 Days	-58.72 percentage change of events Interval -100.0 to 9166.67
Percentage Change in Partial Seizure Frequency (All Partial Seizure Types) Between the 8 Week Baseline Period and 4 Week Intervals During the 21 Week Open-label Treatment Period. >140 Days	-85.42 percentage change of events Interval -100.0 to 12344.44

SECONDARY outcome

Timeframe: last 4 weeks & whole 12 week treatment observation period

Population: Full analysis set(FAS)/intent-to-treat(ITT) all subjects who received \>= 1 dose of study Tx \& \>= 2 partial seizures during baseline pd. LOCF if subjects withdrew then last 4 wks prior to last dose (but after visit 3). 12 wk subjects who withdrew were regarded as missing. n= # subjects evaluable for seizure freedom during defined observation pd.

Count of subjects seizure free during the period.

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Number of Subjects Seizure-free During the last 4 weeks of Obs. period (n=86)	30 participants
Number of Subjects Seizure-free During 12 week Observation period (n=84)	18 participants

SECONDARY outcome

Timeframe: 8 week baseline observation period & last 4 weeks of observation period

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Patients who discontinued less than 4 weeks into the observation period (after Visit 3/week 9) will be regarded as missing. No data prior to week 9 will be used.

Number of subjects with at least a 50% or 75% reduction in partial seizure frequency between baseline and treatment period.

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period. >= 50% reduction	42 participants
Reduction in Partial Seizure Frequency Between Baseline and the Final 4 Weeks of the Observation Period. >= 75% reduction	33 participants

SECONDARY outcome

Timeframe: Day 147 from the first dose of study drug

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period).

Number of subjects achieving seizure freedom (no seizures) during last 4 weeks or duration of 12 week observation period.

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Subjects Achieving Seizure Freedom During Observation Period seizure-free during last 4 weeks	30 participants
Subjects Achieving Seizure Freedom During Observation Period seizure-free during 12 weeks	18 participants

SECONDARY outcome

Timeframe: 8 week baseline observation period & 12 week treatment observation period

Population: Full analysis set (FAS)/intent-to-treat (ITT) (all subjects who received at least 1 dose of study treatment \& minimum 2 partial seizures during baseline pd). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Percentage change from baseline = ((12 weeks - 8 weeks)/8 weeks)*100. Negative mean R-Ratios and associated 95% CIs that do not include zero indicate reduction in partial seizure frequency.

Outcome measures

Measure	Pregabalin n=92 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency Baseline seizure frequency ≤3 per 28 days (n=43)	-33.33 percentage change in events Interval -100.0 to 7566.67
Change in Partial Seizure Frequency (All Partial Seizure Types) Between Baseline and the 12 Week Observation Period Categorized by Baseline Seizure Frequency Baseline seizure frequency >3 per 28 days (n=49)	-21.99 percentage change in events Interval -100.0 to 516.09

SECONDARY outcome

Timeframe: End of 21-week treatment

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment and had a minimum of 2 partial seizures during the baseline period).

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

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) Very Much Improved	14 participants
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) Much Improved	36 participants
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) Minimally Improved	17 participants
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) No Change	9 participants
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) Minimally Worse	3 participants
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) Much Worse	1 participants
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) Very Much Worse	0 participants
Impression of Change in Overall Status Using the Patient Global Impression of Change (PGIC) Missing / Not Done	13 participants

SECONDARY outcome

Timeframe: End of 21-week treatment

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment and had a minimum of 2 partial seizures during the baseline period).

The CGIC is a clinician's judgment of the overall change in the patient's condition over a defined period on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) Very Much Improved	15 partcipants
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) Much Improved	35 partcipants
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) Minimally Improved	24 partcipants
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) No Change	11 partcipants
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) Minimally Worse	4 partcipants
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) Much Worse	2 partcipants
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) Very Much Worse	0 partcipants
Subjects With Categorical Impression of Change in Overall Status Using the Clinical Global Impression of Change (CGIC) Missing / Not Done	2 partcipants

SECONDARY outcome

Timeframe: Baseline, end of 21-week treatment

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). "n" is the number of subjects contributing to the mean at the specified time point.

Subjects recall sleep related activities over the previous 4 weeks. Low scores reflect greater impairment (except sleep adequacy, optimal sleep, &quantity). Range = 0 - 100 for Sleep Disturbance, Snoring, Awaken Short of Breath, Sleep Adequacy, Somnolence, & Sleep Problems Index. Quantity of Sleep Range = 0 - 24. Optimal Sleep Range 0 - 1.

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores Sleep Disturbance (n=72)	-3.95 score on scale 95% Confidence Interval 20.787 • Interval -8.83 to 0.94
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores Awaken Short of Breath (n=77)	-1.82 score on scale Interval -5.93 to 2.29
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores Quantity of Sleep (n=66)	0.05 score on scale Interval -0.33 to 0.42
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores Sleep Adequacy (n=77)	4.29 score on scale Interval -2.2 to 10.77
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores Somnolence (n=77)	0.52 score on scale Interval -4.61 to 5.65
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores Sleep Problems Index (n=72)	-2.81 score on scale Interval -6.5 to 0.88
Changes From Baseline in Medical Outcomes Study (MOS) Sleep Scale Scores Snoring (n=76)	7.89 score on scale Interval 1.97 to 13.82

SECONDARY outcome

Timeframe: Baseline, End of 21-week treatment

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). "n" is the number of subjects contributing to the mean at the specified time point.

Change in total HADS score between Baseline and Week 21. Each of the 14 items is scored 0, 1, 2 or 3 where a score of 3 corresponds to the most anxious/depressed. 7-item depression and 7-item anxiety subscales are summed; each resulting in a total score of 0-21.

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21. HADS Depression Subscale (n=76)	-0.59 score on scale Interval -1.38 to 0.19
Change From Baseline in Hospital Anxiety and Depression Scale(HADS) Depression and Anxiety Symptoms Subscales Between Baseline and Week 21. HADS Anxiety Subscale (n=76)	-1.68 score on scale Interval -2.6 to -0.76

SECONDARY outcome

Timeframe: Baseline, End of 21-week treatment

Population: Safety population (all subjects who had taken at least 1 dose of study drug).

Count of subjects with a weight gain of at least 7 percent relative to baseline.

Outcome measures

Measure	Pregabalin n=98 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline Weight gain ≥7% to <10%	8 participants
Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline Weight gain ≥10% to <15%	2 participants
Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline Weight gain ≥15% to <20%	2 participants
Number of Subjects With a Weight Gain at End of Treatment of at Least 7% Relative to Baseline Weight gain ≥20%	1 participants

SECONDARY outcome

Timeframe: Baseline, End of 21-week treatment

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period).

Number of subjects that responded optimal or non-optimal sleep in Optimal Sleep subscale of Medical Outcomes Study (MOS) Sleep scale.

Outcome measures

Measure	Pregabalin n=93 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Subjects Assessment of Optimal Sleep Optimal Sleep Baseline, Optimal Sleep Wk21	21 participants
Subjects Assessment of Optimal Sleep Optimal Sleep Baseline, Non-Optimal Sleep Wk21	8 participants
Subjects Assessment of Optimal Sleep Non-Optimal Sleep Baseline, Optimal Sleep Wk21	12 participants
Subjects Assessment of Optimal Sleep Non-Optimal Sleep Baseline, Non-Optimal Sleep Wk21	25 participants

POST_HOC outcome

Timeframe: 8 week baseline period & 12 week treatment observation period

Population: Full analysis set (FAS)/intent-to-treat (ITT) population (all subjects who received at least 1 dose of study treatment \& had a minimum of 2 partial seizures during baseline period). Seizure rate was calculated on last observation carried forward (LOCF) basis, whereby data from last 84 days prior to last dose was used to calculate seizure frequency.

Change from baseline = 12 week treatment observation period seizure frequency rate minus 8 week baseline period seizure frequency rate.

Outcome measures

Measure	Pregabalin n=92 Participants Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period. Simple Partial Seizures (n=47)	0.00 change in median partial seizures Interval -15.5 to 149.67
Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period. Complex Partial Seizures (n=76)	0.00 change in median partial seizures Interval -16.33 to 114.67
Change in Partial Seizure Frequency by Type Between the 8 Week Baseline Period and During the 12 Week Observation Period. Evolve to Secondary Generalized (n=30)	0.00 change in median partial seizures Interval -2.67 to 9.04

Adverse Events

Pregabalin

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pregabalin Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Injury, poisoning and procedural complications Lower Limb Fracture	1.0% 1/98
Nervous system disorders Balance Disorder	1.0% 1/98
Nervous system disorders Convulsion	1.0% 1/98

Other adverse events

Measure	Pregabalin Pregabalin treatment, given as 2 divided doses, was initiated at a dose of 150 mg/day (75 mg BID). Then, based on individual subject response and tolerability, the dosage could have been increased to 300 mg/day after 1 week. The dosage could have been incrementally increased further to 600 mg/day after an additional week. After 9 weeks of treatment, the optimal dose of pregabalin was to be maintained for 3 months (12 week treatment observation period).
Gastrointestinal disorders Constipation	2.0% 2/98
General disorders Asthenia	2.0% 2/98
Investigations Weight Increased	3.1% 3/98
Nervous system disorders Ataxia	2.0% 2/98
Nervous system disorders Convulsion	4.1% 4/98
Nervous system disorders Disturbance in Attention	2.0% 2/98
Nervous system disorders Dizziness	5.1% 5/98
Nervous system disorders Headache	2.0% 2/98
Nervous system disorders Somnolence	20.4% 20/98
Psychiatric disorders Agitation	4.1% 4/98
General disorders Gait Disturbance	3.1% 3/98
General disorders Oedema peripheral	2.0% 2/98

Additional Information

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Phone: 1-800-718-1021

Email: ClinicalTrials.govCallCenter@pfizer.com

Results disclosure agreements

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

Restriction type: OTHER