Once-A-Day Pregabalin For Partial Seizures
Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01262677
Collaborator
(none)
325
82
3
17.4
4
0.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
325 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date
:
Feb 17, 2011
Actual Primary Completion Date
:
Jul 31, 2012
Actual Study Completion Date
:
Aug 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: pregabalin CR 330 mg
|
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
|
| Experimental: pregabalin CR 165 mg
|
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 the remainder of the up-titration and double-blind treatment and taper phases (max 14.5 weeks)
|
| Placebo Comparator: Placebo
|
Drug: placebo
matched to the active drug
|
Outcome Measures
Primary Outcome Measures
- Log Transformed (Loge) 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Treatment Phase [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.
Secondary Outcome Measures
- Percentage of Participants With a ≥50% Reduction in the 28-day Partial Seizure Rate From Baseline During the Double-blind Treatment Phase [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [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 [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 [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 [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 [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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Neurology Clinic, PC | Northport | Alabama | United States | 35476 |
| 2 | NEA Baptist Clinic | Jonesboro | Arkansas | United States | 72401 |
| 3 | Clinical Trials, Inc. | Little Rock | Arkansas | United States | 72205 |
| 4 | Collaborative Neuroscience Network, Inc. | Long Beach | California | United States | 90806 |
| 5 | Viking Clinic Research Center | Murrieta | California | United States | 92562 |
| 6 | Viking Clinical Research Center | Murrieta | California | United States | 92562 |
| 7 | Neurological Research Institute | Santa Monica | California | United States | 90404 |
| 8 | Viking Clinical Research Center | Temecula | California | United States | 92591 |
| 9 | Sarkis Clinical Trials | Gainesville | Florida | United States | 32607 |
| 10 | Optima Neurological Services, LLC | Gainesville | Florida | United States | 32608 |
| 11 | Sleep Disorders Center of Georgia - Gainesville | Gainesville | Georgia | United States | 30501 |
| 12 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 13 | VCMA Comprehensive Epilepsy Center | Wichita | Kansas | United States | 67214 |
| 14 | Via Christi Research | Wichita | Kansas | United States | 67214 |
| 15 | Associates in Neurology, PSC | Lexington | Kentucky | United States | 40513 |
| 16 | Mid Atlantic Headache Institute | Pikesville | Maryland | United States | 21208 |
| 17 | Asheville Neurology Specialists, PA | Asheville | North Carolina | United States | 28806 |
| 18 | Lynn Health Science Institute | Oklahoma City | Oklahoma | United States | 73112 |
| 19 | Mark A. Fisher, M.D.- Private Practice | Oklahoma City | Oklahoma | United States | 73112 |
| 20 | Sooner Clinical Research | Oklahoma City | Oklahoma | United States | 73112 |
| 21 | Veroniqe Sebastian, MD | Oklahoma City | Oklahoma | United States | 73120 |
| 22 | Angelique Barreto, MD | Oklahoma City | Oklahoma | United States | 73135 |
| 23 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 24 | FutureSearch Trials of Neurology | Austin | Texas | United States | 78731 |
| 25 | Scott and White Healthcare-Office of Sponsored Research Administration | Temple | Texas | United States | 76502 |
| 26 | Scott & White Healthcare | Temple | Texas | United States | 76508 |
| 27 | Fundacion Argentina Contra las Enfermedades Neurologicas (FACENE) | Ciudad Autonoma de Buenos Aires | Argentina | C1117ABE | |
| 28 | Clinic of Neurology,Clinical Centar University Sarajevo | Sarajevo | Bosnia and Herzegovina | 71000 | |
| 29 | MBAL Puls AD, Nevrologichno otdelenie | Blagoevgrad | Bulgaria | 2700 | |
| 30 | UMBAL Dr. Georgi Stranski, Vtora nevrologichna klinika | Pleven | Bulgaria | 5800 | |
| 31 | DKTs Akta Medika, Konsultativen kabinet po Nevrologiya | Sevlievo | Bulgaria | 5400 | |
| 32 | MBALNP Sveti Naum EAD, Klinika po nervni bolesti za paroksizmalnite sastoyaniya, | Sofia | Bulgaria | 1113 | |
| 33 | Vtora Mnogoprofilna Bolnitsa za Aktivno Lechenie, Nevrologichno Otdelenie | Sofia | Bulgaria | 1202 | |
| 34 | Litomyslská nemocnice, a.s. | Litomysl | Czechia | 570 14 | |
| 35 | Fakultni Thomayerova nemocnice s poliklinikou,Neurologicka klinika IPVZ/FTNsP | Praha 4 | Czechia | 140 59 | |
| 36 | Neurologicka ambulance | Praha 6 | Czechia | 160 00 | |
| 37 | Epilepsie-Zentrum Bethel | Bielefeld | Germany | 33617 | |
| 38 | Praxis fuer Neurologie und Psychiatrie, Psychotherapie | Bielefeld | Germany | 33647 | |
| 39 | Klinik fuer Epileptologie, Universitaet Bonn | Bonn | Germany | 53105 | |
| 40 | Neuro Consil GmbH | Duesseldorf | Germany | 40212 | |
| 41 | Epilepsieklinik fuer Erwachsene Epilepsiezentrum Kork | Kehl-Kork | Germany | 77694 | |
| 42 | Studienzentrum Dr. Stephan Arnold | Muenchen | Germany | 80638 | |
| 43 | Pamela Youde Nethersole Eastern Hospital | Hong Kong | Hong Kong | ||
| 44 | Department of Medicine, Queen Elizabeth Hospital | Kowloon | Hong Kong | 0 | |
| 45 | Dr. Kennessey Albert Korhaz-Rendelointezet, Neurologiai Osztaly | Balassagyarmat | Hungary | 2660 | |
| 46 | Synexus Magyarorszag Kft. | Budapest | Hungary | 1036 | |
| 47 | Fovarosi Onkormanyzat Uzsoki utcai Korhaza, Ideggyogyaszati Osztaly | Budapest | Hungary | 1145 | |
| 48 | Szent Pantaleon Korhaz Nonprofit Kft., Idegosztaly | Dunaujvaros | Hungary | 2400 | |
| 49 | Lalitha Super Specialities Hospital (P) Ltd. | Guntur | Andhra Pradesh | India | 522 001 |
| 50 | Jagadguru Sri Shivathreeshwara Medical College and Hospital, | Mysore | Karnataka | India | 570004 |
| 51 | Deenanath Mangeshkar Hospital and Research Centre | Pune | Maharashtra | India | 411 004 |
| 52 | Sahyadri Clinical Research & Development Center, | Pune | Maharashtra | India | 411 004 |
| 53 | KEM Hospital Research Centre | Pune | Maharashtra | India | 411 011 |
| 54 | Sahyadri Speciality Hospital | Pune | Maharashtra | India | 411004 |
| 55 | Poona Hospital and Research Centre Department of Neurology | Pune | Maharashtra | India | 411030 |
| 56 | Vidyasagar Institute of Mental Health , Neuro& Allied Sciences, | Nehru Nagar | NEW Delhi | India | 110 065 |
| 57 | Jabatan Neurosains, Pusat Pengajian Sains Perubatan, Universiti Sains Malaysia. | Kubang Kerian | Kelantan | Malaysia | 16150 |
| 58 | Hospital Universiti Sains Malaysia | Kelantan Darul Naim | Malaysia | ||
| 59 | Hospital Kuala Lumpur | Kuala Lumpur | Malaysia | 50586 | |
| 60 | Private Office 201 | Delagación Cuauhtemoc | DF | Mexico | 06700 |
| 61 | Hospital Civil de Guadalajara Fray Antonio Alcalde | Guadalajara | Jalisco | Mexico | 44280 |
| 62 | Hospital Universitario Dr. Jose Eleuterio Gonzalez | Monterrey | Nuevo LEON | Mexico | CP 64460 |
| 63 | Hospital Angeles Culiacan | Culiacan | Sinaloa | Mexico | 80020 |
| 64 | Instituto Biomedico de Investigacion A. C. | Aguascalientes | Mexico | 20127 | |
| 65 | Indywidualna Specjalistyczna Praktyka Lekarska | Gdansk | Poland | 80-266 | |
| 66 | Centrum Neurologii Klinicznej Sp. z o. o. | Krakow | Poland | 31-505 | |
| 67 | Gabinet Lekarski A. Klimek | Lodz | Poland | 90-148 | |
| 68 | Niepubliczny Zaklad Opieki Zdrowotnej IGNIS dr med. Alicja Lobinska | Swidnik | Poland | 21-040 | |
| 69 | Epilepsy Control Institute | San Juan | Puerto Rico | 00923 | |
| 70 | Spitalul Clinic de Urgenta "Prof. Dr. Nicolae Oblu" | Iasi | Jud. Iasi | Romania | 700309 |
| 71 | Cabinet Medical Individual " Dr. Adina Maria Roceanu" | Bucuresti | Romania | 010042 | |
| 72 | Municipal Healthcare Institution City Hospital #5, Neurology Department | Barnaul | Russian Federation | 656045 | |
| 73 | State Medical Institution Republican Clinical Hospital | Kazan | Russian Federation | 420064 | |
| 74 | Central Clinical Hospital #2 N.A. Semashko OAO RZD / Department of Rehabilitation | Moscow | Russian Federation | 107150 | |
| 75 | Pyatigorsk City Hospital #2, Neurology Department, | Pyatigorsk | Russian Federation | 357538 | |
| 76 | State Institution St. Petersburg Psychoneurological Research Institute V.M. Bekhterev of Roszdrav | Saint-Petersburg | Russian Federation | 192019 | |
| 77 | Samara Regional Clinical Hospital M.I. Kalinin, Neurology and Neurosurgery Department | Samara | Russian Federation | 443095 | |
| 78 | Institute for Mental Health | Belgrade | Serbia | 11 000 | |
| 79 | National University Hospital | Singapore | Singapore | 119074 | |
| 80 | Singapore General Hospital | Singapore | Singapore | 169608 | |
| 81 | Khon Kaen University, Faculty of Medicine, Neurology Unit, Department of Medicine | Muang | Khon Kaen | Thailand | 40002 |
| 82 | Neurology Division, Department of Medicine, Pramongkutklao College of Medicine | Bangkok | Thailand | 10400 |
Sponsors and Collaborators
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
ClinicalTrials.gov Identifier:
NCT01262677
Other Study ID Numbers:
- A0081194
- 2010-019035-35
First Posted:
Dec 17, 2010
Last Update Posted:
Jan 25, 2021
Last Verified:
Apr 1, 2018
Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Period Title: Overall Study | |||
| STARTED | 100 | 113 | 110 |
| COMPLETED | 91 | 98 | 98 |
| NOT COMPLETED | 9 | 15 | 12 |
Baseline Characteristics
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 of all reporting groups |
| Overall Participants | 100 | 113 | 110 | 323 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
37.88
(13.10)
|
39.58
(13.15)
|
38.72
(13.25)
|
38.76
(13.14)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
53
53%
|
55
48.7%
|
61
55.5%
|
169
52.3%
|
| Male |
47
47%
|
58
51.3%
|
49
44.5%
|
154
47.7%
|
Outcome Measures
| Title | Log Transformed (Loge) 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 112 | 109 |
| Baseline |
2.24
(0.757)
|
2.33
(0.873)
|
2.32
(0.910)
|
| Week 14 |
1.84
(1.003)
|
1.80
(1.030)
|
1.93
(1.132)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: loge (baseline 28-day seizure rate + 1) as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR). 88 participants in each group (264 total) should have provided approximately 90% power. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9076 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference |
| Estimated Value | -0.99 | |
| Confidence Interval |
(2-Sided) 95% -16.28 to 17.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: loge (baseline 28-day seizure rate + 1) as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR). 88 participants in each group (264 total) should have provided approximately 90% power. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0907 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference |
| Estimated Value | -13.05 | |
| Confidence Interval |
(2-Sided) 95% -26.07 to 2.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
| Title | Percentage of Participants With a ≥50% Reduction in the 28-day Partial Seizure Rate From Baseline During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 98 | 111 | 109 |
| Responder |
37.8
37.8%
|
45.9
40.6%
|
35.8
32.5%
|
| Non-responder |
62.2
62.2%
|
54.1
47.9%
|
64.2
58.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | A 2-sided Cochran-Mantel-Haenszel test stratified by geographical region (U.S., Europe, Asia, or Rest of the World) was used to calculate the p-value. No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.752 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | A 2-sided Cochran-Mantel-Haenszel test stratified by geographical region (U.S., Europe, Asia, or Rest of the World) was used to calculate the p-value. No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.125 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Percentage Change From Baseline in 28-day Partial Seizure Rate During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 98 | 111 | 109 |
| Least Squares Mean (Standard Error) [ln (seizures per 28 days)] |
-15.00
(11.668)
|
-31.54
(10.772)
|
-5.70
(10.918)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model was used to calculate the p-value. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5404 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -9.30 | |
| Confidence Interval |
(2-Sided) 95% -39.16 to 20.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model was used to calculate the p-value. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0786 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -25.84 | |
| Confidence Interval |
(2-Sided) 95% -54.64 to 2.97 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
| Title | Frequency of Secondary Generalized Tonic-clonic Seizures (SGTC) During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 98 | 111 | 109 |
| Mean (Standard Deviation) [seizures per 28 days] |
3.99
(8.667)
|
4.43
(14.736)
|
7.51
(24.979)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | A generalized linear model accounting for treatment and geographical region as fixed effects and baseline seizure frequency as a covariate was used to calculate the p-value. This generalized linear model assumed that the SGTC seizure frequency was from a Poisson distribution with a canonical log link function. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6073 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | Generalized linear model (GLM) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.53 to 0.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | A generalized linear model accounting for treatment and geographical region as fixed effects and baseline seizure frequency as a covariate was used to calculate the p-value. This generalized linear model assumed that the SGTC seizure frequency was from a Poisson distribution with a canonical log link function. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4109 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | GLM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 95% -0.53 to 0.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Log Transformed 28-day SGTC Rate for All SGTCs During the Double-blind Maintenance Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 96 | 110 | 109 |
| Least Squares Mean (Standard Error) [ln (seizures per 28 days)] |
0.46
(0.049)
|
0.48
(0.045)
|
0.48
(0.046)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: loge (baseline 28-day seizure rate + 1) as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8268 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.38 | |
| Confidence Interval |
(2-Sided) 95% -12.97 to 11.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: loge (baseline 28-day seizure rate + 1) as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9024 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% -10.69 to 13.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
| Title | Percentage of Participants With ≥50% Reduction in 28-day SGTC Seizure Rate From Baseline During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 96 | 108 | 105 |
| Number [percentage of participants] |
1.0
1%
|
1.9
1.7%
|
1.9
1.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | A 2-sided Cochran-Mantel-Haenszel test stratified by geographical region (U.S., Europe, Asia, or Rest of the World) wtih percentage of responders summarized by treatment group was used to calculate the p-value. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.670 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | A 2-sided Cochran-Mantel-Haenszel test stratified by geographical region (U.S., Europe, Asia, or Rest of the World) wtih percentage of responders summarized by treatment group was used to calculate the p-value. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.927 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Loge 28-day Seizure Rate for All Partial Onset Seizures During the Double-blind Maintenance Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 96 | 110 | 109 |
| Least Squares Mean (Standard Error) [ln(28-day seizure rate)] |
1.91
(0.070)
|
1.77
(0.064)
|
1.88
(0.065)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: loge (baseline 28-day seizure rate + 1) as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8034 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 2.28 | |
| Confidence Interval |
(2-Sided) 95% -14.37 to 22.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: loge (baseline 28-day seizure rate + 1) as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1905 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -10.78 | |
| Confidence Interval |
(2-Sided) 95% -24.81 to 5.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Value is percent reduction in seizures relative to placebo. | |
| Title | Change From Baseline in Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
-0.8
(3.34)
|
-0.4
(3.19)
|
-0.5
(3.13)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: HADS-A baseline score as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR). No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4650 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: HADS-A baseline score as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR). No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9692 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Hospital Anxiety and Depression Scale - Depression (HADS-D) Total Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
-0.5
(3.16)
|
-0.8
(3.49)
|
-0.1
(3.17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: HADS-D baseline score as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR). No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2693 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 0.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: HADS-D baseline score as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR). No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1893 |
| Comments | Statistical testing was done at 95% confidence intervals, two-sided, least square means and their standard errors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
-3.9
(19.89)
|
-1.5
(17.93)
|
-1.9
(14.10)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep disturbance score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7347 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -5.2 to 3.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep disturbance score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8971 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -4.0 to 4.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in MOS-SS - Snoring Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 92 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
-3.5
(25.44)
|
5.4
(26.00)
|
-0.6
(22.71)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: snoring score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3972 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.7 | |
| Confidence Interval |
(2-Sided) 95% -9.1 to 3.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: snoring score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0319 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 6.7 | |
| Confidence Interval |
(2-Sided) 95% 0.6 to 12.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in MOS-SS - Awaken Short of Breath or With Headache Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
0.2
(20.75)
|
1.0
(24.48)
|
-0.8
(18.96)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: awaken short of breath or with headache score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7708 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 95% -4.4 to 5.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: awaken short of breath or with headache score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3560 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 2.4 | |
| Confidence Interval |
(2-Sided) 95% -2.7 to 7.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in MOS-SS - Quantity of Sleep (Hours) at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 92 | 103 | 100 |
| Mean (Standard Deviation) [hours] |
0.2
(1.31)
|
-0.1
(1.18)
|
-0.1
(1.25)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: quantity of sleep at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1129 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: quantity of sleep at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9388 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in MOS-SS - Sleep Adequacy Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
2.3
(31.14)
|
-1.7
(31.44)
|
-1.5
(24.55)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep adequacy score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9053 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -7.5 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep adequacy score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6371 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -8.5 to 5.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in MOS-SS - Sleep Somnolence Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
-0.5
(17.29)
|
5.2
(19.42)
|
5.0
(18.72)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep somnolence score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0119 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -6.4 | |
| Confidence Interval |
(2-Sided) 95% -11.4 to -1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep somnolence score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9909 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -4.9 to 4.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in MOS-SS - Sleep Problems Index I Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
-2.2
(16.91)
|
0.4
(16.43)
|
0.3
(12.62)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep problems index I score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5903 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -5.0 to 2.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep problems index I score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7126 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Problems Index II Score at Week 14 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 101 |
| Mean (Standard Deviation) [units on a scale] |
-2.4
(15.62)
|
0.7
(14.53)
|
0.7
(11.30)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep problems index II score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2431 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -2.1 | |
| Confidence Interval |
(2-Sided) 95% -5.8 to 1.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | ANCOVA model with the following fixed terms was used to calculate the p-value: sleep problems index II score at baseline as a coninuous covariate, sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg CR, pregabalin 330 mg CR). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8654 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -3.2 to 3.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Participants Reporting Optimal Sleep on the MOS-SS - Optimal Sleep Subscale |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 93 | 103 | 103 |
| Number [percentage of participants] |
67.7
67.7%
|
60.2
53.3%
|
60.2
54.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 165 mg, Placebo |
|---|---|---|
| Comments | Logistic regression model was used to calculate the p-value, with the fixed effects for sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR), average hours per night of sleep at baseline as a coninuous covariate, and optimal sleep at Week 14 as dependent variable. No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3241 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.36 | |
| Confidence Interval |
(2-Sided) 95% 0.74 to 2.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 330 mg, Placebo |
|---|---|---|
| Comments | Logistic regression model was used to calculate the p-value, with the fixed effects for sites pooled by geographic region (ie, U.S., Europe, Asia, rest of the world), and treatment group (placebo, pregabalin 165 mg controlled-release (CR), pregabalin 330 mg CR), average hours per night of sleep at baseline as a coninuous covariate, and optimal sleep at Week 14 as dependent variable. No adjustments for multiplicity were taken. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8932 |
| Comments | Statistical testing was done at alpha = 0.05 level, two-sided. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.96 | |
| Confidence Interval |
(2-Sided) 95% 0.54 to 1.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Benefit, Satisfaction, and Willingness to Continue Measure (BSW): Benefit From Treatment Question |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 112 | 109 |
| No |
12.0
12%
|
17.9
15.8%
|
22.0
20%
|
| Little benefit |
31.0
31%
|
23.2
20.5%
|
33.0
30%
|
| Much benefit |
54.0
54%
|
56.3
49.8%
|
42.2
38.4%
|
| Not done |
2.0
2%
|
1.8
1.6%
|
1.8
1.6%
|
| Missing |
1.0
1%
|
0.9
0.8%
|
0.9
0.8%
|
| Title | BSW: Satisfaction From Treatment Question |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 112 | 109 |
| No |
13.0
13%
|
17.9
15.8%
|
23.9
21.7%
|
| Yes |
84.0
84%
|
80.4
71.2%
|
73.4
66.7%
|
| Missing |
3.0
3%
|
1.8
1.6%
|
2.8
2.5%
|
| Title | BSW: Willingness to Continue Question |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 112 | 109 |
| No |
18.0
18%
|
22.3
19.7%
|
26.6
24.2%
|
| Yes |
79.0
79%
|
75.9
67.2%
|
70.6
64.2%
|
| Missing |
3.0
3%
|
1.8
1.6%
|
2.8
2.5%
|
| Title | Percentage of Participants With New or Intensified Physical Examination Findings During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 113 | 110 |
| General |
1.0
1%
|
2.7
2.4%
|
0.0
0%
|
| Skin |
2.0
2%
|
6.2
5.5%
|
4.5
4.1%
|
| Head |
1.0
1%
|
1.8
1.6%
|
0.0
0%
|
| Ears |
3.0
3%
|
1.8
1.6%
|
0.9
0.8%
|
| Eyes |
1.0
1%
|
2.7
2.4%
|
3.6
3.3%
|
| Nose |
0.0
0%
|
0.0
0%
|
1.8
1.6%
|
| Throat |
0.0
0%
|
0.0
0%
|
1.8
1.6%
|
| Lungs |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Heart |
1.0
1%
|
0.0
0%
|
0.0
0%
|
| Abdomen |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Extremities |
2.0
2%
|
2.7
2.4%
|
1.8
1.6%
|
| Other |
14.0
14%
|
7.1
6.3%
|
10.9
9.9%
|
| Title | Percentage of Participants With New or Intensified Neurological Examination Findings During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 113 | 110 |
| None |
79.0
79%
|
78.8
69.7%
|
68.2
62%
|
| Any |
21.0
21%
|
21.2
18.8%
|
31.8
28.9%
|
| Coordination |
1.0
1%
|
1.8
1.6%
|
1.8
1.6%
|
| Cranial nerve function |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
| Cranial nerve II |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Cranial nerve III |
0.0
0%
|
0.0
0%
|
1.8
1.6%
|
| Cranial nerve V |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Cranial nerve VII |
1.0
1%
|
0.0
0%
|
0.9
0.8%
|
| Cranial nerve VIII |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
| Cranial nerve XI |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Deep tendon reflexes |
3.0
3%
|
1.8
1.6%
|
2.7
2.5%
|
| Gait and station |
0.0
0%
|
0.0
0%
|
0.9
0.8%
|
| Level of consciousness |
0.0
0%
|
0.0
0%
|
0.9
0.8%
|
| Mental state |
1.0
1%
|
1.8
1.6%
|
1.8
1.6%
|
| Motor function |
1.0
1%
|
2.7
2.4%
|
3.6
3.3%
|
| Muscle strength |
2.0
2%
|
0.0
0%
|
1.9
1.7%
|
| Pain sensation |
0.0
0%
|
0.0
0%
|
1.9
1.7%
|
| Reflexes |
1.0
1%
|
0.9
0.8%
|
1.9
1.7%
|
| Vibration |
11.1
11.1%
|
10.8
9.6%
|
12.0
10.9%
|
| Title | Percentage of Participants With Self-injurious or Suicidal Ideation or Behavior on Columbia Classification Algorithm of Suicide Assessment (C-CASA) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 113 | 110 |
| Suicide attempt (Lifetime prior to Screening) |
2.0
2%
|
1.8
1.6%
|
5.5
5%
|
| PAISB (Lifetime prior to Screening) |
1.0
1%
|
1.8
1.6%
|
4.5
4.1%
|
| Suicidal ideation (Lifetime prior to Screening) |
11.0
11%
|
10.6
9.4%
|
14.5
13.2%
|
| SIB-NSI (Lifetime prior to Screening) |
1.0
1%
|
0.9
0.8%
|
0.9
0.8%
|
| Suicide attempts at Week 0 |
1.0
1%
|
0.9
0.8%
|
0.0
0%
|
| PAISB at Week 0 |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
| Suicidal ideation at Week 0 |
8.0
8%
|
7.1
6.3%
|
2.7
2.5%
|
| SIB-NSI at Week 0 |
1.0
1%
|
0.0
0%
|
0.0
0%
|
| Suicidal ideation at Week 14 |
4.0
4%
|
2.7
2.4%
|
1.8
1.6%
|
| Title | Percentage of Participants With a Relevant Increase in Sitting Blood Pressure (BP) From Baseline During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 99 | 110 | 108 |
| Maximum increase in systolic BP ≥30 mmHg |
1.0
1%
|
1.8
1.6%
|
0.9
0.8%
|
| Maximum increase in diastolic BP ≥20 mmHg |
5.1
5.1%
|
5.5
4.9%
|
2.8
2.5%
|
| Title | Percentage of Participants With Corrected QT (QTc) Interval Greater Than or Equal to 450 ms |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 113 | 110 |
| Maximum QTcB 450 - <480 |
8.0
8%
|
5.3
4.7%
|
10.0
9.1%
|
| Maximum QTcB 480 - <500 |
1.0
1%
|
0.0
0%
|
0.9
0.8%
|
| Maximum QTcB ≥500 |
0.0
0%
|
1.8
1.6%
|
0.0
0%
|
| Maximum QTcF 450 - <480 |
3.0
3%
|
2.7
2.4%
|
3.6
3.3%
|
| Maximum QTcF 480 - <500 |
1.0
1%
|
0.0
0%
|
0.0
0%
|
| Maximum QTcF ≥500 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Title | Percentage of Participants With Relevant ECG Interval-increases From Baseline During the Double-blind Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 100 | 113 | 110 |
| Max PR interval rise:%change≥25/50% |
1.1
1.1%
|
1.0
0.9%
|
2.1
1.9%
|
| Max QRS complex rise:%change≥25/50% |
1.1
1.1%
|
1.9
1.7%
|
1.0
0.9%
|
| Max. QTcB interval rise: 30≤x<60 |
5.4
5.4%
|
1.9
1.7%
|
3.1
2.8%
|
| Max. QTcB interval rise: ≥60 |
0.0
0%
|
1.9
1.7%
|
0.0
0%
|
| Max. QTcF interval rise: 30≤x<60 |
3.2
3.2%
|
1.9
1.7%
|
2.1
1.9%
|
| Max. QTcF interval rise: ≥60 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Title | Percentage of Participants With Laboratory Test Abnormalities During the Study |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 99 | 111 | 108 |
| Hemoglobin (HGB) <0.8xLLN , |
1.0
1%
|
0.9
0.8%
|
0.9
0.8%
|
| Hematocrit (HCT) <0.8xLLN |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
| RBC Count <0.8xLLN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Platelets <0.5xLLN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Platelets >1.75xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| WBC Count <0.6xLLN |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
| White Blood Cell Count >1.5xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Lymphocytes (absolute) <0.8xLLN |
4.2
4.2%
|
0.9
0.8%
|
1.9
1.7%
|
| Lymphocytes (absolute) >1.2xULN |
2.1
2.1%
|
1.8
1.6%
|
3.8
3.5%
|
| Lymphocytes (%) <0.8xLLN |
0.0
0%
|
0.0
0%
|
1.9
1.7%
|
| Lymphocytes (%) >1.2xULN |
1.0
1%
|
0.0
0%
|
0.9
0.8%
|
| Neutrophils (absolute) <0.8xLLN |
3.1
3.1%
|
1.8
1.6%
|
1.9
1.7%
|
| Neutrophils (absolute) >1.2xULN |
0.0
0%
|
0.0
0%
|
1.9
1.7%
|
| Neutrophils (%) <0.8xLLN |
1.0
1%
|
0.0
0%
|
0.0
0%
|
| Neutrophils (%) >1.2xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Basophils (absolute) >1.2xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Basophils (%) >1.2xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Eosinophils (absolute) >1.2xULN |
3.1
3.1%
|
3.7
3.3%
|
1.9
1.7%
|
| Eosinophils (%) >1.2xULN |
6.3
6.3%
|
4.6
4.1%
|
3.8
3.5%
|
| Monocytes (absolute) >1.2xULN |
0.0
0%
|
1.8
1.6%
|
0.0
0%
|
| Monocytes (%) >1.2xULN |
1.0
1%
|
0.0
0%
|
0.0
0%
|
| Total Bilirubin >1.5xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| AST >3.0xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| ALT >3.0xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Alkaline Phosphatase >3.0xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Total Protein <0.8xLLN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Total Protein >1.2xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Albumin <0.8xLLN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Albumin >1.2xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| BUN >1.3xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Creatinine >1.3xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Uric Acid >1.2xULN |
1.0
1%
|
0.9
0.8%
|
0.0
0%
|
| Sodium <0.95xLLN |
1.0
1%
|
0.0
0%
|
0.0
0%
|
| Sodium >1.05xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Potassium <0.9xLLN |
2.0
2%
|
0.0
0%
|
0.0
0%
|
| Potassium >1.1xULN |
1.0
1%
|
0.0
0%
|
0.0
0%
|
| Chloride <0.9xLLN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Chloride >1.1xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Calcium <0.9xLLN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Calcium >1.1xULN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Glucose <0.6xLLN |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Glucose >1.5xULN |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
| Urine Specific Gravity <1.003 |
0.0
0%
|
1.9
1.7%
|
1.0
0.9%
|
| Urine Specific Gravity >1.030 |
1.1
1.1%
|
1.9
1.7%
|
4.8
4.4%
|
| Urine pH <4.5 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Urine pH >8 |
1.1
1.1%
|
1.9
1.7%
|
1.9
1.7%
|
| Urine Glucose (qualitative) ≥1 |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
| Urine Ketones (qualitative) ≥1 |
2.1
2.1%
|
1.9
1.7%
|
1.9
1.7%
|
| Urine Protein (qualitative) ≥1 |
3.2
3.2%
|
2.8
2.5%
|
1.0
0.9%
|
| Urine Blood/Hgb (qualitative) ≥1 |
8.5
8.5%
|
9.4
8.3%
|
9.5
8.6%
|
| Urine Nitrite ≥1 |
11.7
11.7%
|
5.7
5%
|
13.3
12.1%
|
| Urine RBC ≥20 |
13.3
13.3%
|
0.0
0%
|
9.5
8.6%
|
| Urine WBC ≥20 |
4.8
4.8%
|
3.7
3.3%
|
29.6
26.9%
|
Adverse Events
| Time Frame | 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. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||
| Arm/Group Title | Pregabalin 165 mg | Pregabalin 330 mg | Placebo | |||
| Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
| Pregabalin 165 mg | Pregabalin 330 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Pregabalin 165 mg | Pregabalin 330 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/100 (5%) | 5/113 (4.4%) | 2/110 (1.8%) | |||
| Infections and infestations | ||||||
| Bronchitis | 1/100 (1%) | 0/113 (0%) | 0/110 (0%) | |||
| Pneumonia | 1/100 (1%) | 0/113 (0%) | 0/110 (0%) | |||
| Subcutaneous abscess | 0/100 (0%) | 1/113 (0.9%) | 0/110 (0%) | |||
| Viral infection | 1/100 (1%) | 0/113 (0%) | 0/110 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Wound | 0/100 (0%) | 0/113 (0%) | 1/110 (0.9%) | |||
| Nervous system disorders | ||||||
| Ataxia | 0/100 (0%) | 1/113 (0.9%) | 0/110 (0%) | |||
| Complex partial seizures | 1/100 (1%) | 0/113 (0%) | 0/110 (0%) | |||
| Convulsion | 1/100 (1%) | 1/113 (0.9%) | 1/110 (0.9%) | |||
| Epilepsy | 1/100 (1%) | 0/113 (0%) | 0/110 (0%) | |||
| Grand mal convulsion | 1/100 (1%) | 0/113 (0%) | 0/110 (0%) | |||
| Myoclonus | 0/100 (0%) | 1/113 (0.9%) | 0/110 (0%) | |||
| Somnolence | 0/100 (0%) | 1/113 (0.9%) | 0/110 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 0/100 (0%) | 1/113 (0.9%) | 0/110 (0%) | |||
| Hallucination | 0/100 (0%) | 1/113 (0.9%) | 0/110 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Pregabalin 165 mg | Pregabalin 330 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/100 (14%) | 21/113 (18.6%) | 3/110 (2.7%) | |||
| General disorders | ||||||
| Fatigue | 3/100 (3%) | 6/113 (5.3%) | 1/110 (0.9%) | |||
| Investigations | ||||||
| Weight increased | 1/100 (1%) | 7/113 (6.2%) | 0/110 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 11/100 (11%) | 11/113 (9.7%) | 2/110 (1.8%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
ClinicalTrials.gov Identifier:
NCT01262677
Other Study ID Numbers:
- A0081194
- 2010-019035-35
First Posted:
Dec 17, 2010
Last Update Posted:
Jan 25, 2021
Last Verified:
Apr 1, 2018