Approximately 30% percent of subjects with partial seizures are refractory to treatment with single or combination antiepileptic drugs. The present study will compare the efficacy of two different dosages of pregabalin CR dosed once daily as compared to placebo, when used as adjunctive therapy in subjects requiring adjunctive therapy for partial onset epilepsy, using a randomized, parallel group design.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
325
Controlled Release Tablets, 82.5 mg, once per day (QD) for 3 days
Controlled Release Tablets, 165 mg, once per day (QD) for 11 days
Controlled Release Tablets, 330 mg, once per day (QD) for the remainder of the double-blind treatment phase (max is 12 weeks)
Log Transformed (Loge) 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Treatment Phase
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.
Time frame: Week 0 to Week 14
Percentage of Participants With a ≥50% Reduction in the 28-day Partial Seizure Rate From Baseline During the Double-blind Treatment Phase
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.
Time frame: Week 0 to Week 14
Percentage Change From Baseline in 28-day Partial Seizure Rate During the Double-blind Treatment Phase
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.
Time frame: Week 0 to Week 14
Frequency of Secondary Generalized Tonic-clonic Seizures (SGTC) During the Double-blind Treatment Phase
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Controlled Release Tablets, 165 mg, once per day (QD) for 7 days
Controlled Release Tablets, 82.5 mg, once per day (QD) for 3 days
Controlled Release Tablets, 165 mg, once per day (QD) for the remainder of the up-titration and double-blind treatment and taper phases (max 14.5 weeks)
matched to the active drug
Neurology Clinic, PC
Northport, Alabama, United States
NEA Baptist Clinic
Jonesboro, Arkansas, United States
Clinical Trials, Inc.
Little Rock, Arkansas, United States
Collaborative Neuroscience Network, Inc.
Long Beach, California, United States
Viking Clinic Research Center
Murrieta, California, United States
Viking Clinical Research Center
Murrieta, California, United States
Neurological Research Institute
Santa Monica, California, United States
Viking Clinical Research Center
Temecula, California, United States
Sarkis Clinical Trials
Gainesville, Florida, United States
Optima Neurological Services, LLC
Gainesville, Florida, United States
...and 72 more locations
Time frame: Week 0 to Week 14
Log Transformed 28-day SGTC Rate for All SGTCs During the Double-blind Maintenance Phase
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.
Time frame: Week 2 to Week 14
Percentage of Participants With ≥50% Reduction in 28-day SGTC Seizure Rate From Baseline During the Double-blind Treatment Phase
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.
Time frame: Week 0 to Week 14
Loge 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Maintenance Phase
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.
Time frame: Week 2 to Week 14
Change From Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in Hospital Anxiety and Depression Scale - Depression (HADS-D) Total Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in MOS-SS - Snoring Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in MOS-SS - Awaken Short of Breath or With Headache Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in MOS-SS - Quantity of Sleep (Hours) at 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.
Time frame: Baseline, Week 14
Change From Baseline in MOS-SS - Sleep Adequacy Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in MOS-SS - Sleep Somnolence Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in MOS-SS - Sleep Problems Index I Score at 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.
Time frame: Baseline, Week 14
Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Problems Index II Score at 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.
Time frame: Baseline, Week 14
Percent of Participants Reporting Optimal Sleep on the MOS-SS - Optimal Sleep Subscale
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.
Time frame: Week 14
Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question
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.
Time frame: Week 14
BSW: Satisfaction From Treatment Question
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.
Time frame: Week 14
BSW: Willingness to Continue Question
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.
Time frame: Week 14
Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase
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.
Time frame: Day 1 to Week 15
Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase
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.
Time frame: Day 1 to Week 15
Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA)
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.
Time frame: Week -8 (Screening), Week 0 (Baseline), and Week 14 (double-blind treatment phase)
Percentage of Participants With a Relevant Increase in Sitting Blood Pressure (BP) From Baseline During the Double-blind Treatment Phase
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).
Time frame: Day 1 to Week 15
Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms
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.
Time frame: Week 15
Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase
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.
Time frame: Week 15
Percentage of Participants With Laboratory Test Abnormalities During the Study
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
Time frame: Day 1 to Week 15