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Once-A-Day Pregabalin For Partial Seizures

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ClinicalTrials.gov Identifier: NCT01262677
Recruitment Status : Completed
First Posted : December 17, 2010
Results First Posted : June 5, 2018
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE December 16, 2010
First Posted Date  ICMJE December 17, 2010
Results First Submitted Date  ICMJE October 16, 2017
Results First Posted Date  ICMJE June 5, 2018
Last Update Posted Date June 5, 2018
Actual Study Start Date  ICMJE February 17, 2011
Actual Primary Completion Date July 31, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
Log Transformed (Loge) 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Treatment Phase [ Time Frame: Week 0 to Week 14 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 16, 2010)
The primary endpoint will be the log transformed (loge) 28 day seizure rate for all partial onset seizures collected during the double blind maintenance treatment phase. [ Time Frame: Week 2 to week 14 ]
Change History Complete list of historical versions of study NCT01262677 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • Percentage of Participants With a ≥50% Reduction in the 28-day Partial Seizure Rate From Baseline During the Double-blind Treatment Phase [ Time Frame: Week 0 to Week 14 ]
    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.
  • Percentage Change From Baseline in 28-day Partial Seizure Rate During the Double-blind Treatment Phase [ Time Frame: Week 0 to Week 14 ]
    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.
  • Frequency of Secondary Generalized Tonic-clonic Seizures (SGTC) During the Double-blind Treatment Phase [ Time Frame: Week 0 to Week 14 ]
    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.
  • Log Transformed 28-day SGTC Rate for All SGTCs During the Double-blind Maintenance Phase [ Time Frame: Week 2 to Week 14 ]
    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.
  • Percentage of Participants With ≥50% Reduction in 28-day SGTC Seizure Rate From Baseline During the Double-blind Treatment Phase [ Time Frame: Week 0 to Week 14 ]
    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.
  • Loge 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Maintenance Phase [ Time Frame: Week 2 to Week 14 ]
    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.
  • Change From Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in Hospital Anxiety and Depression Scale - Depression (HADS-D) Total Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in MOS-SS - Snoring Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in MOS-SS - Awaken Short of Breath or With Headache Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in MOS-SS - Quantity of Sleep (Hours) at Week 14 [ Time Frame: 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.
  • Change From Baseline in MOS-SS - Sleep Adequacy Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in MOS-SS - Sleep Somnolence Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in MOS-SS - Sleep Problems Index I Score at Week 14 [ Time Frame: 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.
  • Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Problems Index II Score at Week 14 [ Time Frame: 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.
  • Percent of Participants Reporting Optimal Sleep on the MOS-SS - Optimal Sleep Subscale [ Time Frame: 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.
  • Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question [ Time Frame: 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.
  • BSW: Satisfaction From Treatment Question [ Time Frame: 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.
  • BSW: Willingness to Continue Question [ Time Frame: 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.
  • Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase [ Time Frame: 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). Clinically significant physical examination abnormalities were considered as adverse events based on investigator's discretion.
  • Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase [ Time Frame: 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.
  • Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) [ Time Frame: 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.
  • Percentage of Participants With a Relevant Increase in Sitting Blood Pressure (BP) From Baseline During the Double-blind Treatment Phase [ Time Frame: 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).
  • Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms [ Time Frame: 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.
  • Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase [ Time Frame: 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.
  • Percentage of Participants With Laboratory Test Abnormalities During the Study [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2010)
  • Evaluation for safety using adverse event data, medical history, PHQ 8, laboratory data, physical exams, vital signs, neurological exams, electrocardiograms, and suicidality assessment. [ Time Frame: Screening to Week 15 ]
  • Responder rate (proportion of subjects who have a greater than or equal to 50% reduction in partial seizure rate from baseline during the double blind maintenance treatment phase compared to the 8 week baseline (screening) seizure phase). [ Time Frame: Screening to Week 15 ]
  • The percentage change in 28 day partial seizure rates summarized by treatment group. [ Time Frame: Screening to Week 15 ]
  • Frequency of secondary generalized tonic clonic seizures (SGTC). [ Time Frame: Screening to Week 15 ]
  • Log-transformed 28 day SGTC rate for all SGTCs collected during the double blind maintenance treatment phase. [ Time Frame: Screening to Week 15 ]
  • SGTC responder rate. [ Time Frame: Screening to Week 15 ]
  • Changes from baseline in the anxiety and depression subscale scores of the Hospital Anxiety and Depression Scale (HADS) scores. [ Time Frame: Baseline to Week 14 ]
  • Change from baseline in Medical Outcomes Study Sleep Scale (MOS Sleep Scale) subscale scores. [ Time Frame: Baseline to Week 14 ]
  • Global scores on the patient rated Benefit, Satisfaction, and Willingness to Continue Measure (BSW). [ Time Frame: Baseline to Week 14 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Once-A-Day Pregabalin For Partial Seizures
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multi-center Trial Of Pregabalin Controlled Release Formulation As Adjunctive Therapy In Adults With Partial Onset Seizures
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Partial Seizures
  • Epilepsies, Partial
Intervention  ICMJE
  • Drug: pregabalin
    Controlled Release Tablets, 82.5 mg, once per day (QD) for 3 days
  • Drug: pregabalin
    Controlled Release Tablets, 165 mg, once per day (QD) for 11 days
  • Drug: pregabalin
    Controlled Release Tablets, 330 mg, once per day (QD) for the remainder of the double-blind treatment phase (max is 12 weeks)
  • Drug: pregabalin
    Controlled Release Tablets, 165 mg, once per day (QD) for 7 days
  • Drug: pregabalin
    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)
  • Drug: placebo
    matched to the active drug
Study Arms  ICMJE
  • Experimental: pregabalin CR 330 mg
    Interventions:
    • Drug: pregabalin
    • Drug: pregabalin
    • Drug: pregabalin
    • Drug: pregabalin
  • Experimental: pregabalin CR 165 mg
    Interventions:
    • Drug: pregabalin
    • Drug: pregabalin
  • Placebo Comparator: Placebo
    Intervention: Drug: placebo
Publications * French J, Brandt C, Friedman D, Biton V, Knapp L, Pitman V, Chew M, Dubrava S, Posner HB. Adjunctive use of controlled-release pregabalin in adults with treatment-resistant partial seizures: a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014 Aug;55(8):1220-8. doi: 10.1111/epi.12690. Epub 2014 Jun 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 3, 2018)
325
Original Estimated Enrollment  ICMJE
 (submitted: December 16, 2010)
333
Actual Study Completion Date  ICMJE August 1, 2012
Actual Primary Completion Date July 31, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of epilepsy with partial onset seizures (seizures may be simple or complex, with or without evolution into a bilateral, convulsive seizure)
  • Currently taking 1 to 3 anti-epilepsy medicines (AEDs) at stable dosages, and who have taken at least 2 prior (or ongoing) AEDs

Exclusion Criteria:

  • Primary generalized seizures (for example, absence, myoclonic seizures or Lennox-Gastaut Syndrome)
  • Status epilepticus within one year prior to screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Mexico,   Argentina,   Bosnia and Herzegovina,   Bulgaria,   Czechia,   Germany,   Hong Kong,   Hungary,   India,   Malaysia,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Singapore,   Thailand,   United States
Removed Location Countries Croatia,   Czech Republic,   South Africa
 
Administrative Information
NCT Number  ICMJE NCT01262677
Other Study ID Numbers  ICMJE A0081194
2010-019035-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP