| CTRI Number |
CTRI/2010/091/001213 [Registered on: 07/09/2010] |
| Last Modified On: |
03/10/2014 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Efficacy and Safety of BGG492 as Adjunctive Treatment in Patients With Partial Onset Seizures |
|
Scientific Title of Study
|
A 12-week, Multi-center, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study Examining Seizure Frequency of BGG492 Capsules administrated orally
three times daily (TID) as Adjunctive Treatment in Patients With Partial Onset Seizures |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CBGG492A2207 |
Protocol Number |
| NCT01147003 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
Not Applicable
N/A
India |
| Phone |
|
| Fax |
|
| Email |
|
|
Details of Contact Person
Scientific Query
|
| Name |
Dr. Kamala Rai |
| Designation |
|
| Affiliation |
|
| Address |
Novartis Healthcare Private Limited, Medical Department,
Sandoz House, Shiv Sagar Estate, Dr. Annie Besant Road, Worli,
Mumbai
MAHARASHTRA
400 018
India |
| Phone |
022 -24958533 |
| Fax |
022 -24954112 |
| Email |
kamala.rai@novartis.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr. Kamala Rai |
| Designation |
|
| Affiliation |
|
| Address |
Novartis Healthcare Private Limited, Medical Department,
Sandoz House, Shiv Sagar Estate, Dr. Annie Besant Road, Worli,
Mumbai
MAHARASHTRA
400 018
India |
| Phone |
022 -24958533 |
| Fax |
022 -24954112 |
| Email |
kamala.rai@novartis.com |
|
|
Source of Monetary or Material Support
|
| Novartis Pharma AG, Basel, Switzerland |
|
Primary Sponsor
Modification(s)
|
| Name |
Novartis Health care Private Limited |
| Address |
Novartis India Limited 5th Floor, Sandoz House, Dr Annie Beseant Road, Worli,Mumbai- 400018 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. Chandrashekhar Meshram |
Brain and Mind Institute |
B-101, Neeti Gaurav Complex,Central Bazaar Road, Ramdaspeth-440010
Nagpur
MAHARASHTRA |
0091-712-2428701
0091-712-2451626
|
| Dr. Manoj Gulhane |
Curie Manavata Cancer Centre |
Opp. Mahamarg Bus stand,Mumbai Naka-422 004
|
0091-253-2592666
0091-253-2318993
mngulhane@hotmail.com |
| Dr. Satish Jain |
Indian Epilepsy Centre |
D-61 Hauz-Khas,-110016
New Delhi
DELHI |
0091-11-2653 4465
0091-11-2653 4464
satjain55@hotmail.com |
| Dr. Sudhir Kothari |
Poona Hospital and Research Centre |
Department of Neurology, 27,Sadashiv Path-
Pune
MAHARASHTRA |
9822719440
0091-20-24320681
sudhirkothari@gmail.com |
| Dr. Anshu Rohatgi |
Sir GangaRam Hospital |
Department of Neurology, 4th Floor,Old Rajinder Nagar,-110 002
New Delhi
DELHI |
0091- 11-42251439
0091-11-45041726
rohatgianshu@yahoo.com |
| Dr. Ajit Roy |
St. John's Medical College Hospital |
Department of Neurology,,Sarjapur Road,-560 034
Bangalore
KARNATAKA |
0091-80 22065000
0091-80-25634479
rroy_ajit@hotmail.com |
| Dr. Shamsher Dwivedi |
Vidyasagar Institute of Mental Health and Neuro-Sciences (VIMHANS) |
No.1 Institutional Area,Nehru Nagar,-110 065
New Delhi
DELHI |
0091-11 29849035
0091-11-29849036
sdclinical@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| Central India Medical Research Ethics Committee, Nagpur |
Submittted/Under Review |
| Ethics Committee Poona Hospital and Research Center, Pune |
Submittted/Under Review |
| Ethics Committee VIMHANS |
Approved |
| Independent Ethics Committee, Mumbai |
Submittted/Under Review |
| Independent Ethics Committee, New Delhi |
Approved |
| Institutional Ethical Review Board, Bangalore |
Submittted/Under Review |
| Manavta Clinical Research Institute Professional Ethics Committee, Mumbai |
Submittted/Under Review |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Partial Onset Seizures, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
BGG492 |
5 microgram immediate release capsule |
| Intervention |
BGG492 |
50 microgram immediate release capsule |
| Comparator Agent |
Placebo |
Capsule |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Day(s) |
| Age To |
65.00 Day(s) |
| Gender |
Both |
| Details |
1.Male and female outpatients age 18 to 65 years (inclusive)
2. Are of greater than or equal to 50 kg (110 lb) of weight
3. Have a diagnosis of epilepsy (greater than or equal to 2 years prior to screening) with partial seizures with or
without secondarily generalized seizures according to the International League Against
Epilepsys Classification of Epileptic Seizures (ILAE, 1981)
Appendix 5
The Diagnosis should have been established by clinical history and electroencephalogram
(EEG) that is consistent with localization related epilepsy.
Must have had either a computed tomography (CT) or magnetic resonance imaging (MRI)
within the 5 years prior to screening that ruled out progressive neurological changes (e.g.
Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis); in addition, no physical
examination changes suggestive of such lesions or diseases should have occurred since the
imaging procedure;
If a patient has not had a CT or MRI within the past 5 years, then a MRI must be
performed during the screening period and the results must be reviewed for compliance
with above criterion prior to randomization;
5. Must have uncontrolled partial seizures despite having been treated with at least two
different anti-epileptic drugs within the last 2 years prior to screening (given concurrently
or sequentially);
6. Must have at least 4 partial seizures (defined as simple partial seizures with motor signs,
7. complex partial seizures, complex partial seizures with secondary generalization or a
combination of these types) during the 4-week prospective baseline period and the 4
weeks immediately preceding the baseline period (retrospective and/or prospective data)
7. Have no 28 day seizure free period during the 8 weeks preceding randomization
8. Must be receiving stable treatment (see inclusion criteria 8.1 8.4 and 9) with 1 or a
maximum of 2 AEDs from the list presented below:
8.1 No change in medication type, dose or frequency for 8 weeks prior to
randomization: Carbamazepine, Eslicarbazepine, Oxcarbazepine, Phenytoin,
Valproate, Lacosamide, Lamotrigine, Levetiracetam, Clobazam, Topiramate,
Zonisamide, Gabapentin and Pregabalin
8.2 No change in medication type, dose or frequency for 12 weeks prior to
randomization: Phenobarbital and Primidone
8.3 Vagal nerve stimulation (VNS) will be counted as 1 AED
8.4 Stable benzodiazepine treatment (no change in medication type, dose, or frequency
for 12 weeks prior to randomization) administered for e.g. epilepsy, anxiety, or
sleep disorders will be counted as one AED
Note: The use of intermittent benzodiazepines is defined in exclusion criteria 2.5
refer to Section 4.2.
9. If using a vagal nerve stimulator, the device must have been implanted for at least 22
weeks prior to randomization. Stimulator parameters may not have been changed within 8
weeks prior to randomization
10. Patients having had pre-surgical evaluations may be included. Also, patients having had
brain surgery for partial seizures may be included, if surgery was performed greater than or equal to 1 year
before randomization
11. Are on stable doses (constant for 4 weeks prior to randomization) of non-AED
concomitant medication
12. Have a history of taking his or her medication(s) as directed (determined by direct
questioning of patient, caregiver and or investigator knowledge of prior compliance
problems if the patient had been under the investigator’s care prior to the study)
13. Are reliable and willing to make themselves available for the study period and are able to
record seizures and report adverse events themselves or have a caregiver (parent, legal
guardian) who can record and report the events for them;
14. Have provided written informed consent before any assessments are performed.
|
|
| ExclusionCriteria |
| Details |
Any of the following seizure conditions:
1.1 Presence of only non-motor simple partial seizures
1.2 History of psychogenic seizures
1.3 Absences, myoclonic seizures e.g. in the context of primary generalized epilepsy
1.4 Previous history of Lennox-Gastaut syndrome
1.5 History of status epilepticus or seizure clusters (where individual seizures cannot
be counted according to the judgment of the investigator) occurring within 52
weeks prior to randomization
1.6 Only seizures caused by an underlying medical illness during the 52 weeks prior to
randomization
2. Have been treated with
2.1 Felbamate, unless treatment has been continuous for greater than or equal to 2 years
2.2 Vigabatrin during the 26 weeks prior to randomization
2.3 Monoamine oxidase (MAO) inhibitors, tricyclic-antidepressants and narcotic
analgesics such as e.g. morphine, oxycodone, fentanyl, codeine within 8 weeks
prior to randomization
2.4 Barbiturates (except for seizure control) within 8 weeks prior to randomization
2.5 Intermittent benzodiazepines two or more times in a 4-week period prior to
randomization (1-2 doses over a 24-hr period will be considered one-time use)
2.6 L-dopa formulations
2.7 Use of concomitant medication that are potential inhibitors of OATP transporters
e.g. cyclosporine, rifampin, fluvastatine, fexofenadine 8 weeks prior to
randomization
Known history of hypersensitivity to the study drug or to drugs of similar chemical classes
(e.g. sulfonamides)
4. Have had multiple drug allergies or one or more severe drug reactions to an AED,
including dermatological reactions, (e.g. Stevens-Johnson syndrome, hematological, or
organ toxicity reactions) a rash would not be exclusionary
5. Use of other investigational drugs within 12 weeks prior to randomization
6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a negative
hCG laboratory test (greater than or equal to 5mIU per mL) at screening and a negative urine test immediately prior
to administering the first dose of study medication
7. Women of childbearing potential, defined as all women physiologically capable of
becoming pregnant including women whose partners have been sterilized by vasectomy or
other means, UNLESS they are
• Women whose career, lifestyle, or sexual orientation precludes intercourse with a male
partner
• Using two birth control methods. The two methods can be a double barrier method or
a barrier method in combination with a hormonal method
Adequate barrier methods of contraception include diaphragm, condom (by the
partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal
contraceptives include any marketed contraceptive agent that includes an estrogen
and or a progestational agent.
Reliable contraception should be started at screening, maintained throughout the study
and for 2 week after study drug discontinuation.
Women are considered post menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous
amenorrhea with serum FSH levels greater than 40 mIU per mL [for US only: and estradiol less than 20 pg per mL]
or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six
weeks ago. In the case of oophorectomy alone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she considered not
of child bearing potential.
8. Any of the following cardiovascular conditions
8.1 Myocardial infarction and or cerebrovascular accident (CVA or stroke) within 26
weeks prior to screening
8.2 History of or unstable angina pectoris at Screening or Baseline
8.3 Hypertension uncontrolled by medication (defined as supine systolic blood
pressure greater than or equal to 160 mmHg, or diastolic blood pressure greater than or equal to 100 mmHg) at screening or
baseline or if re-assessed as abnormal according to the above stated limits at prior
to initial dosing on Day 1 |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Seizure counts, documenting the percent change in seizure frequency of BGG492 in the maintenance period. |
28 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| 1) Responder rate: analysis of patients with a 50% or greater reduction in seizure frequency of BGG492 during the maintenance period. |
28 days |
|
Target Sample Size
Modification(s)
|
Total Sample Size="126"
Sample Size from India="0"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
Date Missing |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
15/06/2010 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Completed |
| Recruitment Status of Trial (India) |
|
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Target number of patients is 35.
Planned FPFV from India is 23 Sep 2010. |