Study Of The Safety And Efficacy Of Lyrica In The Treatment Of Newly Diagnosed Partial Epilepsy

A Randomized, Comparative, Double-Blind, Parallel-Group, Multicenter, Monotherapy, Study Of Pregabalin (Lyrica) And Lamotrigine (Lamictal) In Patients With Newly Diagnosed Partial Seizures

The purpose of this study is to assess whether Lyrica is a safe and effective treatment for partial epilepsy in comparison with an established treatment, Lamictal.

Study Overview

• Status: Completed
• Conditions: Epilepsy, Partial
• Intervention / Treatment: Drug: Pregabalin; Drug: Lamotrigine

• Study Type: Interventional
• Enrollment (Actual): 660
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • Pfizer Investigational Site
  • Bruxelles, Belgium, 1070
    • Pfizer Investigational Site
  • Leuven, Belgium, 3000
    • Pfizer Investigational Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Pfizer Investigational Site
  • Sofia, Bulgaria, 1113
    • Pfizer Investigational Site
  • Sofia, Bulgaria, 1309
    • Pfizer Investigational Site
  • Sofia, Bulgaria, 1524
    • Pfizer Investigational Site
  • Varna, Bulgaria, 9010
    • Pfizer Investigational Site
• China
  • Cheng Du Si Chaun, China, 610041
    • Pfizer Investigational Site
  • Chongqing, China, 400016
    • Pfizer Investigational Site
  • Tian Jin, China, 300052
    • Pfizer Investigational Site
  • Shanxi
    • Xi'an, Shanxi, China, 710032
      • Pfizer Investigational Site
• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Pfizer Investigational Site
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia
      • Pfizer Investigational Site
• Czechia
  • Brno 2, Czechia, 602 00
    • Pfizer Investigational Site
  • Hradec Kralove, Czechia, 500 05
    • Pfizer Investigational Site
  • Ostrava, Czechia, 708 58
    • Pfizer Investigational Site
  • Pelhrimov, Czechia, 393 01
    • Pfizer Investigational Site
  • Praha 4, Czechia, 140 59
    • Pfizer Investigational Site
  • Rychnov nad Kneznou, Czechia, 516 01
    • Pfizer Investigational Site
  • Zlin, Czechia, 760 01
    • Pfizer Investigational Site
• Estonia
  • Tallinn, Estonia, 10138
    • Pfizer Investigational Site
  • Tartu, Estonia, 51014
    • Pfizer Investigational Site
• Finland
  • Kuopio, Finland, 70210
    • Pfizer Investigational Site
  • Tampere, Finland, 33520
    • Pfizer Investigational Site
• France
  • Bordeaux Cedex, France, 33076
    • Pfizer Investigational Site
  • Nancy Cedex, France, 54035
    • Pfizer Investigational Site
  • Strasbourg Cedex, France, 67091
    • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 10365
    • Pfizer Investigational Site
  • Bonn, Germany, 53105
    • Pfizer Investigational Site
  • Essen, Germany, 45147
    • Pfizer Investigational Site
  • Frankfurt, Germany, 60528
    • Pfizer Investigational Site
  • Ulm, Germany, 89075
    • Pfizer Investigational Site
  • Ulm, Germany, 89081
    • Pfizer Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Pfizer Investigational Site
  • Kowloon, Hong Kong
    • Pfizer Investigational Site
  • Shatin, Hong Kong
    • Pfizer Investigational Site
• Hungary
  • Budapest, Hungary, 1145
    • Pfizer Investigational Site
  • Gyor, Hungary, 9023
    • Pfizer Investigational Site
  • Nyiregyhaza, Hungary, 4400
    • Pfizer Investigational Site
• India
  • Bangalore, India, 560 034
    • Pfizer Investigational Site
  • Lucknow, India, 226 014
    • Pfizer Investigational Site
  • New Delhi, India, 110 002
    • Pfizer Investigational Site
  • Karnataka
    • Bangalore, Karnataka, India, 560 054
      • Pfizer Investigational Site
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452001
      • Pfizer Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600 006
      • Pfizer Investigational Site
• Ireland
  • Dublin
    • Tallaght, Dublin, Ireland, 24
      • Pfizer Investigational Site
• Italy
  • Bologna, Italy, 40139
    • Pfizer Investigational Site
  • Firenze, Italy, 50125
    • Pfizer Investigational Site
  • Foggia, Italy, 71100
    • Pfizer Investigational Site
  • Pisa, Italy, 56126
    • Pfizer Investigational Site
• Korea, Republic of
  • Daejeon, Korea, Republic of, 301-721
    • Pfizer Investigational Site
  • Gwangju, Korea, Republic of, 501-757
    • Pfizer Investigational Site
  • Incheon, Korea, Republic of, 405-760
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 120-752
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 138-736
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 134-701
    • Pfizer Investigational Site
• Latvia
  • Riga, Latvia, LV 1002
    • Pfizer Investigational Site
  • Riga, Latvia, LV 1038
    • Pfizer Investigational Site
• Lithuania
  • Kaunas, Lithuania, 50009
    • Pfizer Investigational Site
  • Vilnius, Lithuania, 08661
    • Pfizer Investigational Site
  • Vilnius, Lithuania, 03215
    • Pfizer Investigational Site
• Mexico
  • San Luis Potosi, Mexico, 78223
    • Pfizer Investigational Site
  • DF
    • Mexico, DF, Mexico, 14000
      • Pfizer Investigational Site
• Netherlands
  • ZH
    • Den Haag, ZH, Netherlands, 2512 VA
      • Pfizer Investigational Site
• Norway
  • Lillehammer, Norway, 2629
    • Pfizer Investigational Site
  • Trondheim, Norway, 7006
    • Pfizer Investigational Site
• Portugal
  • Amadora, Portugal, 2700-276
    • Pfizer Investigational Site
  • Coimbra, Portugal, 3000-548
    • Pfizer Investigational Site
  • Coimbra, Portugal, 3040-853 Coimbra
    • Pfizer Investigational Site
  • Porto, Portugal, 4099-001
    • Pfizer Investigational Site
  • Porto, Portugal, 4200-319
    • Pfizer Investigational Site
• Romania
  • Bucuresti, Romania, 050098
    • Pfizer Investigational Site
  • Bucuresti, Romania, 11461
    • Pfizer Investigational Site
  • Jud. Cluj
    • Cluj-Napoca, Jud. Cluj, Romania, 400012
      • Pfizer Investigational Site
• Singapore
  • Singapore, Singapore, 169608
    • Pfizer Investigational Site
• Slovakia
  • Bratislava, Slovakia, 82606
    • Pfizer Investigational Site
  • Bratislava, Slovakia, 833 05
    • Pfizer Investigational Site
  • Bratislava, Slovakia, 813 69
    • Pfizer Investigational Site
  • Kosice, Slovakia, 04015
    • Pfizer Investigational Site
  • Zilina, Slovakia, 012 07
    • Pfizer Investigational Site
• Spain
  • Girona, Spain, 17007
    • Pfizer Investigational Site
  • Madrid, Spain, 28040
    • Pfizer Investigational Site
  • Valencia, Spain, 46009
    • Pfizer Investigational Site
  • Valencia, Spain, 46014
    • Pfizer Investigational Site
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Pfizer Investigational Site
• Sweden
  • Goteborg, Sweden, 413 45
    • Pfizer Investigational Site
  • Linkoping, Sweden, 581 85
    • Pfizer Investigational Site
  • Uppsala, Sweden, 75185
    • Pfizer Investigational Site
• Taiwan
  • Tainan, Taiwan
    • Pfizer Investigational Site
  • Taipei, Taiwan, 112
    • Pfizer Investigational Site
  • Taipei, Taiwan
    • Pfizer Investigational Site
• Thailand
  • Bangkok, Thailand, 10400
    • Pfizer Investigational Site
  • Bangkok
    • Rajthevee, Bangkok, Thailand, 10400
      • Pfizer Investigational Site
  • Khon Kaen
    • Muang, Khon Kaen, Thailand, 40002
      • Pfizer Investigational Site
• United Kingdom
  • Glasgow, United Kingdom, G11 6NT
    • Pfizer Investigational Site
  • Liverpool, United Kingdom, L9 7LJ
    • Pfizer Investigational Site
  • Treliske, Truro, Cornwall, United Kingdom, TR1 3LJ
    • Pfizer Investigational Site
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 7LN
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be diagnosed with partial epilepsy and have experienced at least 2 partial seizures (simple partial, complex partial or partial seizure with secondary generalization) in the past year with one in the past 6 months.

Exclusion Criteria:

• Treatable causes of seizures, for example identified etiologies including metabolic, neoplastic or active infectious origin.
• Primary generalized seizures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Pregabalin; dose 150-600 mg/day given BID
Active Comparator: 2	Drug: Lamotrigine; dose 100-500 mg/day given BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Seizure-free Participants (Responders) During Efficacy Assessment Phase	Responders = participants who achieved any 6 consecutive months (>182 days) of seizure-freedom (absence of partial seizures, generalized seizures and unclassified epileptic seizures) during the 52 week efficacy assessment phase.	Week 5 up to Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to 6 Consecutive Months of Seizure-freedom After 4-week Dose Escalation Phase: All Seizures	Time in days, from first day of study medication to the first 6 months of seizure freedom after Day 28. Participants who did not achieve 6 months seizure freedom after Day 28 were censored from analysis.	Week 4 up to Week 56
Exit Due to Adverse Events During the Double-blind Treatment Phase (Including Dose Escalation Phase)	Number of participants who exited the study due to adverse events during the double-blind treatment period. Time in days, from first day of study treatment to day of exit from the study due to an adverse event (ie, last day on study medication) during the double blind treatment period (including dose escalation phase) was inestimable. Observations with other reasons for exiting or participants who did not exit the study were right censored as of the last day on study medication.	Week 0 to Week 56
Exit for Any Reason During the Double-blind Treatment Phase (Including Dose Escalation Phase)	Number of participants who exited the study for any reason during the double blind treatment phase. Time in days, from first day of study treatment to day of exit from the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit the study were right censored as of the last day on study medication.	Week 0 to Week 56
Exit Due to Lack of Efficacy After 4-week Dose Escalation Phase	Number of participants who exited the study due to lack of efficacy after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit due to lack of efficacy after Day 28 of the escalation phase (ie, last day on study medication) was inestimable. Participants who did not exit or exited for a different reason were right censored as of the last day on study medication.	Week 4 up to Week 56
Exit Due to Any Reason After 4-week Dose Escalation Phase	Number of participants who exited the study due to any reason after the 4-week dose escalation phase. Time in days, from first day of study treatment to day of exit after Day 28 of the study due to any reason (ie, last day on study medication) was inestimable. Participants who did not exit or did not reach this phase were right censored as of the last day on study medication.	Week 4 up to Week 56
Time to First Seizure After the 4-Week Dose Escalation Phase	Time in days, from first day of study treatment to the day of first seizure after Day 28 of the escalation phase (ie, last day on study medication). Participants who did not reach this phase or who did not have a seizure after Day 28 were right censored from the analysis as of the last day on study medication.	Week 4 up to Week 56
Median Monthy Seizure Frequency: All Partial Seizures	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).	Baseline up to Week 60
Mean Monthy Seizure Frequency: All Partial Seizures	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).	Baseline up to Week 60
Median Monthy Seizure Frequency: All Seizures	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).	Baseline up to Week 60
Mean Monthy Seizure Frequency: All Seizures	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Month of time = number of months after Week 4 (Dose Escalation).	Baseline up to Week 60
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.	Month 1 through Month 9 (after 6 months seizure freedom achieved)
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Partial Seizures	All partial seizures include complex partial seizures, simple partial seizures, and partial seizures evolving to secondarily generalized seizures. Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.	Month 1 through Month 9 (after 6 months seizure freedom achieved)
Median Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.	Month 1 through Month 9 (after 6 months seizure freedom achieved)
Mean Monthy Seizure Frequency of Responders for the Months After Achieving 6 Consecutive Months of Seizure Freedom: All Seizures	Seizure frequency based on 28-day seizure rate: number (#) of seizures in period (month) divided by # days in period minus # of missing diary days in period * 28. Responder = participant who achieved at least 6 months of seizure freedom after Week 4 and up to Week 56. Monthly seizure frequency measured from day of achievement of 6 months of seizure freedom.	Month 1 through Month 9 (after 6 months seizure freedom achieved)
Percentage of Participants Who Achieved at Least 6 Consecutive Months of Seizure Freedom (Responders) by Final Dosage Levels and Treatment Group	Responder = participant who achieved at least 6-months of seizure freedom (all seizures) after Week 4, and up to Week 56. Dose Level defined as last total-daily-dose received after Week 4, and up to Week 56.	Week 5 up to Week 56
Change From Baseline to Week 56 in Hospital Anxiety and Depression Scale (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; 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 symptoms. Scores relative to start of randomized treatment.	Baseline to Week 56
Medical Outcomes Study Sleep Scale (MOS-SS): Optimal Sleep Subscale	MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Optimal Sleep subscale is derived from sleep quantity average hours of sleep each night during the past week. Number of subjects with response Optimal if sleep quantity was 7 or 8 hours of sleep per night, and Non-optimal if average sleep was less than or greater than 7 to 8 hours per night. Analysis assesses the MOS-Sleep scale relative to the start of randomized treatment.	Week 8, Week 32, and Week 56

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Kwan P, Brodie MJ, Kalviainen R, Yurkewicz L, Weaver J, Knapp LE. Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial. Lancet Neurol. 2011 Oct;10(10):881-90. doi: 10.1016/S1474-4422(11)70154-5. Epub 2011 Aug 31.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: January 18, 2006
• First Submitted That Met QC Criteria: January 18, 2006
• First Posted (Estimate): January 20, 2006

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Epilepsy; partial seizures; pregabalin monotherapy; double-blind and randomized trial; lamotrigine comparator
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lamotrigine; Pregabalin
• Other Study ID Numbers: A0081046