CTRI/2025/01/078928 [Registered on: 17/01/2025] Trial Registered Prospectively
Last Modified On:
04/05/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
Study to
Evaluate the Efficacy and Safety Levetiracetam in Patients with
Epilepsy
Scientific Title of Study
A Double-Blind, Randomized, Placebo and Active Controlled Study to
Evaluate the Efficacy and Safety of Once Daily, Extended Release
Levetiracetam as Add-on Therapy in Patients with Refractory Partial Onset
Epilepsy
Niramaya Hospital Survey No. 4742 Behind Jai Hind Petrol pump Next, Chinchwad Station Rd, MIDC, Chinchwad, Pimpri-Chinchwad, Maharashtra 411019 India Chandrapur MAHARASHTRA
919860918000 919860918000 amitpande411@gmail.com
G Sree Ranga Lakshmi
Osmania General Hospital
Room no. 1, Department of Neurology, Osmania General Hospital, QQDC Building, 2nd floor, Afzal Gunj Road, Hyderabad-500012, Telangana Hyderabad TELANGANA
9866193700
rangalakshmi2000@gmail.com
Dr Ashis Das
Peerless Hospitex Hospital And Research Centre Ltd
Room no. 1, Department of Neurology, 360,Panchasayar, Kolkata -700094, West Bengal, Kolkata WEST BENGAL
9830224854 9830224854 drashisdas@gmail.com
Dr Sikandar Adwani
Radiant Superspeciality Hospital
Room no. 1, Department of Neurology, Sabnis Plot, Near, Kalyan Nagar Chowk, Vivekanand Colony, Amravati-Maharashtra- 4444606, India, Amravati Amravati MAHARASHTRA
8446015115 8446015115 drsikandaradwani@gmail.com
Dr Anshu Rohatgi
Sir Ganga Ram Hospital
Sir Ganga Ram Hospital Marg, Rajinder Nagar, New Delhi-110060 New Delhi DELHI
9810159046 9810159046 rohatgianshu@yahoo.com
Dr Bhuma Vengamma
Sri Devaraj Urs Academy of Higher Education & Research.(SDUAHER)
Room no. 2, Department of Neurology, Tamaka, Kolar, Karnataka-563103. Kolar KARNATAKA
9849348530
vicechancellor@sduaher.ac.in
Dr Amit Bhalchandra Yeole
Supe Heart & Diabetes Hospital and Research Centre
Opp. Adhar Ashram, Near Rungta School, Gharpure Ghat, Ashok Stambh, Nashik, Maharashtra – 422002 India Nashik MAHARASHTRA
1) Male and female, between 18 and above years of age, both inclusive.
2) Willingness and capability to provide informed consent form (ICF), be compliant with study
procedures such as eDiary completion, be compliant with background anti-seizure medication
(ASM) and Investigational Medicinal Product (IMP) intake.
3) Diagnosis of epilepsy with Focal-onset seizures (FOS) with or without secondary
generalization according to the International League Against Epilepsy Classification of
epileptic seizures.
4) On stable doses of ASM for at least 4 weeks prior to screening.
5) Confirmed drug-resistant FOS despite 1 to 3 stable ASM with at least 6 seizures during the
8 week observational period.
6) Patients who have Vagal Nerve Stimulator (VNS) must have stable settings more than 3 months prior
to screening and expected to remain unchanged during the duration of the study.
7) Females of childbearing potential, if not abstinent, should use a highly effective double
contraception, started 60 days prior to study entry and 30 days after end of study drug
administration:
a) Oral, injected or implanted hormonal methods of contraception.
b) Intrauterine device (IUD)
c) Barrier methods: condom, diaphragm, spermicidal foam
d) Male partner surgical sterilization (vasectomy)
8) Females of non-childbearing potential: either surgically sterilized (e.g. bilateral tubal ligation),
had undergone hysterectomy or is at least 1 year postmenopausal (amenorrhea duration of at
least 12 months)
9) Sexually active males with partner of childbearing potential commit to use an acceptable
method of birth control consistently and correctly (oral, transdermal, systemic or implant
contraception birth control, intrauterine devices) for 90 days after the last study drug
administration.
ExclusionCriteria
Details
1) Presence of primary generalized epilepsies or seizures, such as absences, myoclonic
epilepsies, Lennox Gastaut syndrome.
2) History of status epilepticus in the past 3 months prior to screening.
3) Seizure clusters where individual seizures cannot be counted.
4) History of non epileptic seizures.
5) Evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, hepatic,
hematologic or renal disease, neoplastic malignancies etc.) that in the opinion of the
investigator could affect the subjects safety or trial conduct.
6) Neurodegenerative and other progressive neurological disorders.
7) Diagnosis of active psychiatric disease, except depressed subjects on stable doses of
selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors for at
least 12 weeks prior to screening.
8) History of prior suicide attempt or imminent risk of self harm based on investigators judgment
or with a yes answer on item 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS).
9) History of drug abuse as defined by Diagnostic and Statistical Manual of Mental
Disorders version 5 (DSM V) and or positive drug screening other than prescribed drugs.
10) Alcohol abuse as per Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM
V) in the past year.
11) Positive for hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) or Human
Immunodeficiency Virus (HIV) infection at screening.
12) Subjects presenting symptoms of coronavirus disease COVID 19.
13) Known allergic reaction or intolerance to levetiracetam or other pyrrolidone derivatives or to
any of the excipients.
14) Participation in a study involving administration of an investigational product within one month
prior to screening or within five half lives of the previous study investigational compound,
whichever is longer.
15) Women who are currently pregnant, who intend to become pregnant during the study, or who
are breastfeeding.
16) Subjects with a diagnosis of Congenital Short QT Syndrome (SQTS). Subjects with a family
history of Congenital Short QT Syndrome (SQTS) or family history of sudden death of
unknown cause.
17) The corrected QT interval by Fredericia (QTcF) more than and equal 450 msec in male and 470 msec in female
subjects.
18) Laboratory values at screening:
Platelets less than 100,000 per mm3
Absolute neutrophil count less than 1500 per mm3
Haemoglobin within 10.0g per dL
Aspartate aminotransferase or alanine aminotransferase more than 3x upper limit of normal
Estimated Glomerular Filtration Rate less than 80
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Assess the reduction in weekly Focal Onset Seizures (FOS) frequency
of levetiracetam extended release (XR) compared to levetiracetam immediate release (IR) in
subjects with drug resistant FOS
Assess the reduction in Focal Onset Seizures (FOS) frequency in 8 Weeks.
Secondary Outcome
Outcome
TimePoints
assess the reduction in weekly FOS frequency of levetiracetam
XR compared to placebo in subjects with drug-resistant FOS.
Change from baseline in absolute FOS over the 12 week double blind period.
Proportion of subjects with at least 50 percentage reduction from baseline in total seizure frequency
per week over the 12 week double blind period.
Proportion of subjects with at least 50% reduction from baseline in total seizures over the
12 week double blind period
Target Sample Size
Total Sample Size="300" Sample Size from India="150" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a double-blind, randomized, placebo and active controlled study three arm to evaluate the efficacy and safety of levetiracetam XR as add-on therapy, in subjects with drug-resistant Focal onset epilepsy. This phase III trial consists of an initial 8-week observational period followed by a 12 week double blind period and a final 2 week safety follow up period . A total of 10 visits are planned for this study, of which 4 will be held by telephone and 6 at the study site. Overall, around 300 subjects will be screened across approximately 78 centres across Europe and India to obtain a total of 255 randomized subjects. Subjects will be randomized in a randomization ratio between levetiracetam IR 1000 mg per day, levetiracetam XR 1000 mg per day and placebo. The randomization will be stratified by age into two groups below 18 years and 18 years. Following screening, subjects will enter the 8 week observation period for the assessment of the seizure frequency to confirm their eligibility. All subjects must be on stable doses of anti-seizure medication for at least 4 weeks prior to the screening visit. Additionally, subjects had to show confirmed drug-resistant focal seizures despite 1 to 3 stable ASM, with at least 6 seizures during the initial 8 week observational period. During the 12 week treatment period, the investigational medicinal products will be administered swallowing the capsule and granules contained in the sachet with a sufficient amount of water, as one capsule in the morning; and one capsule plus one granule sachet at evening for all subjects, with or without food, for masking purposes and irrespective of their treatment arm. Subjects completing the 12 week double blind period will enter the 2 week safety period. Subjects who prematurely discontinue the treatment will complete the early termination visit as soon as possible.