Trial Outcomes & Findings for Once-A-Day Pregabalin For Partial Seizures (NCT NCT01262677)

Last Updated: 2021-01-25

Results Overview

Seizures were recorded and documented in a daily Seizure Diary by the participants, family member, caregiver, or legal guardian. Simple partial seizures without a visible motor component (ie, lacking visible movements during the seizure) were not counted toward eligibility, or in the primary or secondary efficacy analyses. Natural logarithm of the 28-day seizure rate was reported in this outcome measure.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

325 participants

Primary outcome timeframe

Week 0 to Week 14

Results posted on

2021-01-25

Participant Flow

This was a multicenter, multinational study and included four standard phases: an 8-week baseline observation phase, a 2-week dose escalation phase, a 12-week fixed-dose maintenance phase, and a 1-week taper phase.

An 8-week baseline observation phase began immediately after the screening visit. Througout the observation phase the participants continued their current anti-epileptic drugs (AEDs) at the prescribed dosage, eligibility was re-evaluated at Week -4 and Week 0, and the participants recorded all seizures in daily seizure diaries.

Participant milestones

Participant milestones
Measure	Pregabalin 165 mg After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hour (hr) after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Overall Study STARTED	100	113	110
Overall Study COMPLETED	91	98	98
Overall Study NOT COMPLETED	9	15	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin 165 mg After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hour (hr) after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Overall Study Does not meet entrance criteria	0	2	0
Overall Study Insufficient clinical response	0	0	1
Overall Study Lost to Follow-up	1	0	2
Overall Study No longer willing to participate	3	3	2
Overall Study Reason not provided	2	1	3
Overall Study Protocol Violation	0	1	1
Overall Study Adverse Event (AE) related to study drug	3	8	3

Baseline Characteristics

Once-A-Day Pregabalin For Partial Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Total n=323 Participants Total of all reporting groups
Age, Continuous	37.88 years STANDARD_DEVIATION 13.10 • n=99 Participants	39.58 years STANDARD_DEVIATION 13.15 • n=107 Participants	38.72 years STANDARD_DEVIATION 13.25 • n=206 Participants	38.76 years STANDARD_DEVIATION 13.14 • n=7 Participants
Sex: Female, Male Female	53 Participants n=99 Participants	55 Participants n=107 Participants	61 Participants n=206 Participants	169 Participants n=7 Participants
Sex: Female, Male Male	47 Participants n=99 Participants	58 Participants n=107 Participants	49 Participants n=206 Participants	154 Participants n=7 Participants

PRIMARY outcome

Timeframe: Week 0 to Week 14

Population: The intent-to treat (ITT) population consisted of all randomized participants who received at least one dose of double-blind treatment, and had a baseline and at least one follow-up double-blind treatment phase assessment visit. The ITT population was the primary sample and included: Pregabalin 165 mg: 100, Pregabalin 330 mg: 112, Placebo: 109.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=112 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Log Transformed (Loge) 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Treatment Phase Baseline	2.24 ln (seizures per 28 days) Standard Deviation 0.757	2.33 ln (seizures per 28 days) Standard Deviation 0.873	2.32 ln (seizures per 28 days) Standard Deviation 0.910
Log Transformed (Loge) 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Treatment Phase Week 14	1.84 ln (seizures per 28 days) Standard Deviation 1.003	1.80 ln (seizures per 28 days) Standard Deviation 1.030	1.93 ln (seizures per 28 days) Standard Deviation 1.132

SECONDARY outcome

Timeframe: Week 0 to Week 14

Population: The ITT population consisted of all randomized participants who received at least one dose of double-blind treatment, and had a baseline and at least one follow-up double-blind treatment phase assessment visit. The ITT population was the primary sample and included: Pregabalin 165 mg: 100, Pregabalin 330 mg: 112, Placebo: 109.

Seizures were recorded and documented in a daily Seizure Diary by the participants, family member, caregiver, or legal guardian. Simple partial seizures without a visible motor component (ie, lacking visible movements during the seizure) were not counted toward eligibility, or in the primary or secondary efficacy analyses. Participants who had a ≥50% reduction in the 28-day partial seizure rate from baseline were defined as a responder, otherwise they were default as a non-responder.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=98 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=111 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With a ≥50% Reduction in the 28-day Partial Seizure Rate From Baseline During the Double-blind Treatment Phase Responder	37.8 percentage of participants	45.9 percentage of participants	35.8 percentage of participants
Percentage of Participants With a ≥50% Reduction in the 28-day Partial Seizure Rate From Baseline During the Double-blind Treatment Phase Non-responder	62.2 percentage of participants	54.1 percentage of participants	64.2 percentage of participants

SECONDARY outcome

Timeframe: Week 0 to Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=98 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=111 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage Change From Baseline in 28-day Partial Seizure Rate During the Double-blind Treatment Phase	-15.00 ln (seizures per 28 days) Standard Error 11.668	-31.54 ln (seizures per 28 days) Standard Error 10.772	-5.70 ln (seizures per 28 days) Standard Error 10.918

SECONDARY outcome

Timeframe: Week 0 to Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=98 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=111 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Frequency of Secondary Generalized Tonic-clonic Seizures (SGTC) During the Double-blind Treatment Phase	3.99 seizures per 28 days Standard Deviation 8.667	4.43 seizures per 28 days Standard Deviation 14.736	7.51 seizures per 28 days Standard Deviation 24.979

SECONDARY outcome

Timeframe: Week 2 to Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=96 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=110 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Log Transformed 28-day SGTC Rate for All SGTCs During the Double-blind Maintenance Phase	0.46 ln (seizures per 28 days) Standard Error 0.049	0.48 ln (seizures per 28 days) Standard Error 0.045	0.48 ln (seizures per 28 days) Standard Error 0.046

SECONDARY outcome

Timeframe: Week 0 to Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=96 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=108 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=105 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With ≥50% Reduction in 28-day SGTC Seizure Rate From Baseline During the Double-blind Treatment Phase	1.0 percentage of participants	1.9 percentage of participants	1.9 percentage of participants

SECONDARY outcome

Timeframe: Week 2 to Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=96 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=110 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Loge 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Maintenance Phase	1.91 ln(28-day seizure rate) Standard Error 0.070	1.77 ln(28-day seizure rate) Standard Error 0.064	1.88 ln(28-day seizure rate) Standard Error 0.065

SECONDARY outcome

Timeframe: Baseline, Week 14

HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at Week 14	-0.8 units on a scale Standard Deviation 3.34	-0.4 units on a scale Standard Deviation 3.19	-0.5 units on a scale Standard Deviation 3.13

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in Hospital Anxiety and Depression Scale - Depression (HADS-D) Total Score at Week 14	-0.5 units on a scale Standard Deviation 3.16	-0.8 units on a scale Standard Deviation 3.49	-0.1 units on a scale Standard Deviation 3.17

SECONDARY outcome

Timeframe: Baseline, Week 14

Participant-rated 12-item questionnaire to assess key constructs of sleep over the past week. 7 subscales: sleep disturbance, snoring, awakened short of breath or with headache, sleep adequacy, and somnolence (range:0-100); sleep quantity (range:0-24), and optimal sleep (yes: 1, no: 0). 6 and 9 item index measures of sleep disturbance were constructed to provide composite scores. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range \* 100); total score range: 0 to 100; higher score = greater intensity of attribute.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance Score at Week 14	-3.9 units on a scale Standard Deviation 19.89	-1.5 units on a scale Standard Deviation 17.93	-1.9 units on a scale Standard Deviation 14.10

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=92 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in MOS-SS - Snoring Score at Week 14	-3.5 units on a scale Standard Deviation 25.44	5.4 units on a scale Standard Deviation 26.00	-0.6 units on a scale Standard Deviation 22.71

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in MOS-SS - Awaken Short of Breath or With Headache Score at Week 14	0.2 units on a scale Standard Deviation 20.75	1.0 units on a scale Standard Deviation 24.48	-0.8 units on a scale Standard Deviation 18.96

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=92 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=100 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in MOS-SS - Quantity of Sleep (Hours) at Week 14	0.2 hours Standard Deviation 1.31	-0.1 hours Standard Deviation 1.18	-0.1 hours Standard Deviation 1.25

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in MOS-SS - Sleep Adequacy Score at Week 14	2.3 units on a scale Standard Deviation 31.14	-1.7 units on a scale Standard Deviation 31.44	-1.5 units on a scale Standard Deviation 24.55

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in MOS-SS - Sleep Somnolence Score at Week 14	-0.5 units on a scale Standard Deviation 17.29	5.2 units on a scale Standard Deviation 19.42	5.0 units on a scale Standard Deviation 18.72

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in MOS-SS - Sleep Problems Index I Score at Week 14	-2.2 units on a scale Standard Deviation 16.91	0.4 units on a scale Standard Deviation 16.43	0.3 units on a scale Standard Deviation 12.62

SECONDARY outcome

Timeframe: Baseline, Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=101 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Problems Index II Score at Week 14	-2.4 units on a scale Standard Deviation 15.62	0.7 units on a scale Standard Deviation 14.53	0.7 units on a scale Standard Deviation 11.30

SECONDARY outcome

Timeframe: Week 14

Optimal sleep was considered between 7 to 8 hours of average sleep per night inclusive, while average sleep less than or greater than the 7 to 8 hour of average sleep per night was non-optimal.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=93 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=103 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=103 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percent of Participants Reporting Optimal Sleep on the MOS-SS - Optimal Sleep Subscale	67.7 percentage of participants	60.2 percentage of participants	60.2 percentage of participants

SECONDARY outcome

Timeframe: Week 14

The BSW consisted of 3 single-item measures designed to capture the participant's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy. The BSW was read aloud to the participant by the investigator or designated center personnel and then was given to the participant to complete independently.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=112 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question No	12.0 percentage of participants	17.9 percentage of participants	22.0 percentage of participants
Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question Little benefit	31.0 percentage of participants	23.2 percentage of participants	33.0 percentage of participants
Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question Much benefit	54.0 percentage of participants	56.3 percentage of participants	42.2 percentage of participants
Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question Not done	2.0 percentage of participants	1.8 percentage of participants	1.8 percentage of participants
Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question Missing	1.0 percentage of participants	0.9 percentage of participants	0.9 percentage of participants

SECONDARY outcome

Timeframe: Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=112 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
BSW: Satisfaction From Treatment Question No	13.0 percentage of participants	17.9 percentage of participants	23.9 percentage of participants
BSW: Satisfaction From Treatment Question Yes	84.0 percentage of participants	80.4 percentage of participants	73.4 percentage of participants
BSW: Satisfaction From Treatment Question Missing	3.0 percentage of participants	1.8 percentage of participants	2.8 percentage of participants

SECONDARY outcome

Timeframe: Week 14

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=112 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=109 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
BSW: Willingness to Continue Question No	18.0 percentage of participants	22.3 percentage of participants	26.6 percentage of participants
BSW: Willingness to Continue Question Yes	79.0 percentage of participants	75.9 percentage of participants	70.6 percentage of participants
BSW: Willingness to Continue Question Missing	3.0 percentage of participants	1.8 percentage of participants	2.8 percentage of participants

SECONDARY outcome

Timeframe: Day 1 to Week 15

Population: The safety population included all randomized participants who took at least one dose of the study medication. The safety population consisted of: Pregabalin 165 mg: 100, Pregabalin 330 mg: 113, Placebo: 110.

Physical examinations included general appearance (including hight at baseline), vital sign (sitting heart rate and sitting blood pressure), weight, skin (examination for the presence of rash), HEENT (examinatin of head, eyes, ears, nose and throat), chest ausculation of lung fields), cardiovascular (ausculatin of heart sounds (S1 and S2) and for the presence of murmurs, gallops, or rubs), gastrointestinal (abdominal rigidity and tenderness), an extremities (e.g. edema). Clinically significant physical examination abnormalities were considered as adverse events based on investigator's discretion.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Nose	0.0 percentage of participants	0.0 percentage of participants	1.8 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Throat	0.0 percentage of participants	0.0 percentage of participants	1.8 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Lungs	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Heart	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Abdomen	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Extremities	2.0 percentage of participants	2.7 percentage of participants	1.8 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Other	14.0 percentage of participants	7.1 percentage of participants	10.9 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase General	1.0 percentage of participants	2.7 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Skin	2.0 percentage of participants	6.2 percentage of participants	4.5 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Head	1.0 percentage of participants	1.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Ears	3.0 percentage of participants	1.8 percentage of participants	0.9 percentage of participants
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase Eyes	1.0 percentage of participants	2.7 percentage of participants	3.6 percentage of participants

SECONDARY outcome

Timeframe: Day 1 to Week 15

Neurological examinations included level of consciousness, mental status, cranial nerve assessment, muscle strength, reflexes, pin prick and vibratory sensation (the latter using a 128-Hz tuning fork), coordination and gait.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Cranial nerve VII	1.0 percentage of participants	0.0 percentage of participants	0.9 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase None	79.0 percentage of participants	78.8 percentage of participants	68.2 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Any	21.0 percentage of participants	21.2 percentage of participants	31.8 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Coordination	1.0 percentage of participants	1.8 percentage of participants	1.8 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Cranial nerve function	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Cranial nerve II	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Cranial nerve III	0.0 percentage of participants	0.0 percentage of participants	1.8 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Cranial nerve V	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Cranial nerve VIII	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Cranial nerve XI	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Deep tendon reflexes	3.0 percentage of participants	1.8 percentage of participants	2.7 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Gait and station	0.0 percentage of participants	0.0 percentage of participants	0.9 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Level of consciousness	0.0 percentage of participants	0.0 percentage of participants	0.9 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Mental state	1.0 percentage of participants	1.8 percentage of participants	1.8 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Motor function	1.0 percentage of participants	2.7 percentage of participants	3.6 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Muscle strength	2.0 percentage of participants	0.0 percentage of participants	1.9 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Pain sensation	0.0 percentage of participants	0.0 percentage of participants	1.9 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Reflexes	1.0 percentage of participants	0.9 percentage of participants	1.9 percentage of participants
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase Vibration	11.1 percentage of participants	10.8 percentage of participants	12.0 percentage of participants

SECONDARY outcome

Timeframe: Week -8 (Screening), Week 0 (Baseline), and Week 14 (double-blind treatment phase)

C-CASA is described as a standardized suicidal rating system. The C-CASA has eight categories (4 suicidal events: completed suicide, suicide attempt, preparatory act toward imminent suicidal behavior (PAISB), and suicidal ideation; 2 nonsuicidal events: self-injurious behavior, no suicidal intent (SIB-NSI) and other no deliberate self-harm, and 2 indeterminate or potentially suicidal events: self-injurious behavior, suicidal intent unknown and not enough information) that distinguish suicidal events from nonsuicidal events and indeterminate or potentially suicidal events.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) PAISB at Week 0	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) SIB-NSI at Week 0	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) Suicidal ideation (Lifetime prior to Screening)	11.0 percentage of participants	10.6 percentage of participants	14.5 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) SIB-NSI (Lifetime prior to Screening)	1.0 percentage of participants	0.9 percentage of participants	0.9 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) Suicide attempts at Week 0	1.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) Suicidal ideation at Week 0	8.0 percentage of participants	7.1 percentage of participants	2.7 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) Suicidal ideation at Week 14	4.0 percentage of participants	2.7 percentage of participants	1.8 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) Suicide attempt (Lifetime prior to Screening)	2.0 percentage of participants	1.8 percentage of participants	5.5 percentage of participants
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) PAISB (Lifetime prior to Screening)	1.0 percentage of participants	1.8 percentage of participants	4.5 percentage of participants

SECONDARY outcome

Timeframe: Day 1 to Week 15

Physical examinations included general appearance (including hight at baseline), vital sign (sitting heart rate and sitting blood pressure), weight, skin (examination for the presence of rash), HEENT (examinatin of head, eyes, ears, nose and throat), chest (ausculation of lung fields), cardiovascular (ausculatin of heart sounds (S1 and S2) and for the presence of murmurs, gallops, or rubs), gastrointestinal(abdominal rigidity and tenderness), an extremities (e.g. edema).

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=99 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=110 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=108 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With a Relevant Increase in Sitting Blood Pressure (BP) From Baseline During the Double-blind Treatment Phase Maximum increase in systolic BP ≥30 mmHg	1.0 percentage of participants	1.8 percentage of participants	0.9 percentage of participants
Percentage of Participants With a Relevant Increase in Sitting Blood Pressure (BP) From Baseline During the Double-blind Treatment Phase Maximum increase in diastolic BP ≥20 mmHg	5.1 percentage of participants	5.5 percentage of participants	2.8 percentage of participants

SECONDARY outcome

Timeframe: Week 15

The original ECG was reviewed by the investigator and kept on site as part of source documentation. A central ECG reader was also used for this study. QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB) were calculated.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms Maximum QTcB 450 - <480	8.0 percentage of participants	5.3 percentage of participants	10.0 percentage of participants
Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms Maximum QTcB 480 - <500	1.0 percentage of participants	0.0 percentage of participants	0.9 percentage of participants
Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms Maximum QTcB ≥500	0.0 percentage of participants	1.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms Maximum QTcF 450 - <480	3.0 percentage of participants	2.7 percentage of participants	3.6 percentage of participants
Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms Maximum QTcF 480 - <500	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms Maximum QTcF ≥500	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Week 15

The original ECG was reviewed by the investigator and kept on site as part of source documentation. A central ECG reader was also used for this study. 25/50% represents ≥25% or ≥50% increase over baseline respectively, based on cut points. Cut points are 100 ms for QRS and 200 ms for PR.

Outcome measures

Outcome measures
Measure	Pregabalin 165 mg n=100 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase Max PR interval rise:%change≥25/50%	1.1 percentage of participants	1.0 percentage of participants	2.1 percentage of participants
Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase Max QRS complex rise:%change≥25/50%	1.1 percentage of participants	1.9 percentage of participants	1.0 percentage of participants
Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase Max. QTcB interval rise: 30≤x<60	5.4 percentage of participants	1.9 percentage of participants	3.1 percentage of participants
Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase Max. QTcB interval rise: ≥60	0.0 percentage of participants	1.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase Max. QTcF interval rise: 30≤x<60	3.2 percentage of participants	1.9 percentage of participants	2.1 percentage of participants
Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase Max. QTcF interval rise: ≥60	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Day 1 to Week 15

Laboratory samples in hematology, chemistry, and urinalysis were analyzed by a cental laboratory. Any laboratory value that was identified as clinically significant was reported as an AE. LLN: Lower limit of normal, ULN: Uper limit of normal, RBC: Red Blood Cell, WBC: White Blood Cell, AST: Aspartate Aminotransferase, ALT: Alanine Aminotransferase, BUN: Blood Urea Nitrogen

Outcome measures

Adverse Events

Pregabalin 165 mg

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Pregabalin 330 mg

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pregabalin 165 mg n=100 participants at risk After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 participants at risk After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 participants at risk After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Infections and infestations Bronchitis	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Subcutaneous abscess	0.00% 0/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.88% 1/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Viral infection	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Wound	0.00% 0/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.91% 1/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Ataxia	0.00% 0/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.88% 1/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Complex partial seizures	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Convulsion	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.88% 1/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.91% 1/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Epilepsy	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Grand mal convulsion	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Myoclonus	0.00% 0/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.88% 1/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Somnolence	0.00% 0/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.88% 1/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	0.00% 0/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.88% 1/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Hallucination	0.00% 0/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.88% 1/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Other adverse events
Measure	Pregabalin 165 mg n=100 participants at risk After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=113 participants at risk After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=110 participants at risk After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Nervous system disorders Dizziness	11.0% 11/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.7% 11/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.8% 2/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	3.0% 3/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.3% 6/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.91% 1/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	1.0% 1/100 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.2% 7/113 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/110 • From the time the participant provided informed consent, which was obtained prior to the participant's participation in the study, through and including 28 calendar days after the last administration of the investigational product. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one particpant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Pregabalin 165 mg n=99 Participants After the 2-week dose escalation phase, the participants received 165 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Pregabalin 330 mg n=111 Participants After the 2-week dose escalation phase, the participants received 330 mg of pregabalin once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.	Placebo n=108 Participants After the 2-week dose escalation phase, the participants received placebo once a day during the 12-week double-blind maintenance phase. Afterwards, the study medication was tapered for one week. The tablets were to be taken orally, within 1 hr after the evening meal. The medication must have been taken intact and not bitten, chewed, cut, or otherwise altered prior to swallowing.
Percentage of Participants With Laboratory Test Abnormalities During the Study Lymphocytes (%) >1.2xULN	1.0 percentage of participants	0.0 percentage of participants	0.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Neutrophils (absolute) <0.8xLLN	3.1 percentage of participants	1.8 percentage of participants	1.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Neutrophils (%) <0.8xLLN	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Eosinophils (absolute) >1.2xULN	3.1 percentage of participants	3.7 percentage of participants	1.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Calcium >1.1xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine pH <4.5	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine pH >8	1.1 percentage of participants	1.9 percentage of participants	1.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine Ketones (qualitative) ≥1	2.1 percentage of participants	1.9 percentage of participants	1.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine Nitrite ≥1	11.7 percentage of participants	5.7 percentage of participants	13.3 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine RBC ≥20	13.3 percentage of participants	0.0 percentage of participants	9.5 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine WBC ≥20	4.8 percentage of participants	3.7 percentage of participants	29.6 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Hemoglobin (HGB) <0.8xLLN ,	1.0 percentage of participants	0.9 percentage of participants	0.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Hematocrit (HCT) <0.8xLLN	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study RBC Count <0.8xLLN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Platelets <0.5xLLN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Platelets >1.75xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study WBC Count <0.6xLLN	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study White Blood Cell Count >1.5xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Lymphocytes (absolute) <0.8xLLN	4.2 percentage of participants	0.9 percentage of participants	1.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Lymphocytes (absolute) >1.2xULN	2.1 percentage of participants	1.8 percentage of participants	3.8 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Lymphocytes (%) <0.8xLLN	0.0 percentage of participants	0.0 percentage of participants	1.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Neutrophils (absolute) >1.2xULN	0.0 percentage of participants	0.0 percentage of participants	1.9 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Neutrophils (%) >1.2xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Basophils (absolute) >1.2xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Basophils (%) >1.2xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Eosinophils (%) >1.2xULN	6.3 percentage of participants	4.6 percentage of participants	3.8 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Monocytes (absolute) >1.2xULN	0.0 percentage of participants	1.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Monocytes (%) >1.2xULN	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Total Bilirubin >1.5xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Alkaline Phosphatase >3.0xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study AST >3.0xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study ALT >3.0xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Total Protein <0.8xLLN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Total Protein >1.2xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Albumin <0.8xLLN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Albumin >1.2xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study BUN >1.3xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Creatinine >1.3xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Uric Acid >1.2xULN	1.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Sodium <0.95xLLN	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Sodium >1.05xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Potassium <0.9xLLN	2.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Potassium >1.1xULN	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Chloride <0.9xLLN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Chloride >1.1xULN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Calcium <0.9xLLN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Glucose <0.6xLLN	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Glucose >1.5xULN	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine Specific Gravity <1.003	0.0 percentage of participants	1.9 percentage of participants	1.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine Specific Gravity >1.030	1.1 percentage of participants	1.9 percentage of participants	4.8 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine Glucose (qualitative) ≥1	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine Protein (qualitative) ≥1	3.2 percentage of participants	2.8 percentage of participants	1.0 percentage of participants
Percentage of Participants With Laboratory Test Abnormalities During the Study Urine Blood/Hgb (qualitative) ≥1	8.5 percentage of participants	9.4 percentage of participants	9.5 percentage of participants