CTRI/2020/05/025236 [Registered on: 19/05/2020] Trial Registered Prospectively
Last Modified On:
06/03/2021
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A clinical study of Sponsor’s Vigabatrin 500 mg tablets compared to SABRIL® (Vigabatrin) Tablets 500mg to study the pharmacokinetics and safety in adult refractory complex partial-seizure patients.
Scientific Title of Study
A Randomized, Open-Label, Two-Period, Two-Treatment, Two-Sequence, Crossover, Multiple-Dose, Steady State, Multicenter, Bioequivalence Study of Vigabatrin Tablet USP 500 mg of Zydus Worldwide DMCC, United Arab Emirates with Sabril® (Vigabatrin) Tablet 500 mg of Lundbeck, Deerfield, IL 60015, USA in Subjects with Refractory Complex Partial Seizures Under Fasting Condition.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
C2A00012, Version 1.0 dated 04 Mar 2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Associate Vice President - Global Clinical Operations
Affiliation
Cliantha Research
Address
Cliantha Research, Department Clinical Trials, Room no. 01, 2nd floor, 6, Arista@Eight Corporate House, Near Satyam House,
Behind Rajpath Club, Bodakdev, Ahmadabad-380054, Gujarat, India
Ahmadabad GUJARAT 380054 India
Phone
079-66219555
Fax
079-66219549
Email
ddomadia@cliantha.com
Details of Contact Person Scientific Query
Name
Dr Ankesh Barnwal
Designation
Associate Director-I Medical Services
Affiliation
Cliantha Research
Address
Cliantha Research, Department Clinical Trials, Room no. 01, 2nd floor, 6, Arista@Eight Corporate House, Near Satyam House,
Behind Rajpath Club, Bodakdev, Ahmadabad-380054, Gujarat, India
Ahmadabad GUJARAT 380054 India
Phone
079-66219545
Fax
079-66219549
Email
abarnwal@cliantha.com
Details of Contact Person Public Query
Name
Mr Hitesh Maheshwari
Designation
Sr. Project Manager
Affiliation
Cliantha Research
Address
Cliantha Research, Department Clinical Trials, Room no. 01, 2nd floor, 6, Arista@Eight Corporate House, Near Satyam House,
Behind Rajpath Club, Bodakdev, Ahmadabad-380054, Gujarat, India
Ahmadabad GUJARAT 380054 India
Phone
079-66219577
Fax
079-66219549
Email
hmaheshwari@cliantha.com
Source of Monetary or Material Support
Zydus Worldwide DMCC, Unit No : 908, Armada Tower 2, Plot No : JLT-PH2-P2A, Jumeirah Lakes Towers, Dubai, UAE. P.O. BOX – 113536
Primary Sponsor
Name
Zydus Worldwide DMCC
Address
Unit No : 908, Armada Tower 2, Plot No : JLT-PH2-P2A,
Jumeirah Lakes Towers,
Dubai, UAE. P.O. BOX – 113536
3rd Floor, clinical research department, lifepoint multispeciality hospital Pvt. Ltd., 145/1, mumbai-banglore highway, near hotel sayaji, wakad, pune- 411057, maharashtra, india Pune MAHARASHTRA
919767092120
gunjkar.jaykumar118@gmail.com
Dr Praveen Harawat Jain
Medipoint Hospital Pvt. Ltd.,.
3rd floor Medipoint Clinical Building 241/1, New DP Road, Near Sai Heritage, Pentagon Research Aundh, Pune-411007, Maharashtra, India. Pune MAHARASHTRA
9860526808
praveenharawat746@gmail.com
Dr Siddhesh Rajadhyax
Nirmal hospital pvt. ltd.
Nirmal hospital pvt. ltd. 2/1423-8-6 sagrampura ring road near centre point, Surat- 395002, Gujarat, India Surat GUJARAT
919742444220
drsiddheshrajadhyax@gmail.com
Dr Brahme keyur madan
Sir sayajirao general hospital (SSG hospital), medical college baroda
5th floor, male medical ward No. 3, emergency department, sir sayajirao general hospital (SSG hospital), medical college baroda, jail road (indira avenue), anandpura, vadodara- 390001, gujarat, India Ahmadabad GUJARAT
Anand Ethics Committee, Anand Multispeciality Hospital and Research Centre, 4th Floor, Sarthak Mall, Mahatma Mandir Road, Sargasan Cross Road, Gandhinagar-382421
Approved
Institutional Ethics Committee for Human Research, Medical College Baroda, Sir Sayajirao General Hospital (SSG Hospital), Medical College Baroda, Jail Road (Indira Avenue), Anandpura, Vadodara- 390001, Gujarat, India
Submittted/Under Review
LPR Ethics Committee, Lifepoint Multispeciality Hospital Pvt. Ltd., 145/1, Mumbai-Banglore Highway, Near Hotel Sayaji, Wakad, Pune- 411057, Maharashtra, India.
Sabril® (Vigabatrin) Tablet 500 mg of Lundbeck, Deerfield, IL 60015, USA
Patient will be instructed to take Oral dose of either the test product or reference product 500 mg in the morning and evening (i.e. twice daily) at an interval of at least 12 hours (± 30 minutes) between the doses as per the randomization schedule from Day 1 to Day 4 in each period
Intervention
Vigabatrin Tablet USP 500 mg of Zydus Worldwide DMCC, United Arab Emirates
Patient will be instructed to take Oral dose of either the test product or reference product 500 mg in the morning and evening (i.e. twice daily) at an interval of at least 12 hours (± 30 minutes) between the doses as per the randomization schedule from Day 1 to Day 4 in each period.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
55.00 Year(s)
Gender
Both
Details
1) Male or non-pregnant or non-lactating female aged between ≥ 18 to ≤ 55 years with refractory complex partial seizures.
2) The subject has refractory complex partial seizure as evidenced by the attainment of all the following criteria:
a) The subject has failed because of lack of efficacy with 2 or more antiepileptics administered as monotherapy or polytherapy.
b) The subject should be taking at least 1 AED (A vagal nerve stimulator is not counted as an AED)
3) Currently stable on a regimen consisting of Vigabatrin tablet 500 mg twice daily for at least 28 days as adjunctive therapy and likely to continue the same dose in the study.
4) Subject with Body Mass Index (BMI) ≥ 18 to ≤ 30kg/m2. BMI values should be rounded to the nearest integer (e.g. 30.4 rounds down to 30, while 17.5 rounds up to 18).
5) Subject with adequate hematopoietic and liver function defined as:
a) Hemoglobin of ≥ 9.0 g/dL
b) Platelet count ≥ 100,000/mm3
c) AST and ALT ≤ 3 times ULN, Alkaline phosphatase ≤ 2.5 times ULN, Bilirubin ≤ 1.5 times ULN.
6) Subject with a estimsted creatinine clearance of > 80 mL/min.
7) Subject with clinically non-significant findings on ophthalmologic
assessments for visual field and visual acuity.
8) Male and female subjects must agree to use acceptable contraceptive methods from screening to end of study.
9) Willing to provide informed consent to participate in this study.
10) Able to comply with protocol requirements and assessments.
ExclusionCriteria
Details
1) History of hypersensitivity to Vigabatrin or any ingredients of the
formulation.
2) Pre-existing ocular or neurological disease that might affect bilateral visual field or interference with perimetry (e.g. aphakia, visually significant cataract, glaucoma, diabetic retinopathy, ischemic optic neuropathy, multiple sclerosis).
3) Concurrent exposure to medication with known or suspected retinal or optic nerve toxicity (e.g. deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines and ethambutol).
4) Subject with suicidal ideation (score of 4 or 5 on the Columbia Suicide Severity Rating Scale [C-SSRS]) within the past 2 months or any suicidal behavior occurring in the past year.
5) Presence of primary generalized epilepsy or seizures, such as absence seizures and/or myoclonic epilepsy.
6) Subject with peripheral neuropathy.
7) Presence or previous history of Lennox-Gastaut syndrome.
8) A history of status epilepticus within approximately 6 months prior to randomization.
9) A history of psychogenic seizures.
10) Suffering from psychotic disorder(s) and/or unstable recurrent affective disorder(s) evident by use of antipsychotics within the last 2 years.
11) Expected changes in concomitant medications during the period of
study.
12) Ingestion of any alcohol or alcoholic food, caffeine or xanthine containing food or beverage, recreational drugs within the 48 hours prior to first dosing of Day 1 of period I.
13) Consumption of red wine, seville oranges, grapefruit or grapefruit juice, (pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices) within 7 days prior to first dosing of Period I.
14) Presence of a progressive central nervous system CNS disease,including degenerative CNS diseases.
15) Major surgery of the gastrointestinal tract, the liver or kidney within 6 months prior to randomization which may affect the pharmacokinetics of Vigabatrin.
16) Subject unable to swallow orally administered medication or with
gastrointestinal disorders likely to interfere with absorption of the study medication.
17) A positive test result for Hepatitis (includes subtypes B & C), HIV
and/or Syphilis (RPR/VDRL).
18) Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 60 days or difficulty in accessibility of veins.
19) Subject received any investigational drug within the past 30 days of screening.
20) History of drug or alcohol dependency or abuse within the last 2 years of screening.
21) Have had multiple drug allergies or a severe drug reaction to an AED(s), including dermatological (e.g., Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
22) History of any significant cardiovascular, renal, hepatic, neurologic, endocrine dysfunction, inflammatory bowel disease, cancer, or any other condition which in the opinion of the investigator, may put the subject at risk because of participation in the study.
23) Subject who is institutionalized.
24) Any other condition that, in the investigator’s judgment, might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To Analyze Pharmacokinetic parameters.
1. AUC during a dosage interval at steady state.
2. Concentration at the end of the dosing interval.
3. Maximum measured plasma concentration at steady state.
4. The time to maximum plasma concentration at steady state
5. The Average concentration at steady state during a dosing interval
6. Degree of Fluctuation
7. Swing
In each period, on Day 3 (morning & evening) to Day 4 (morning), a pre-dose blood sample.
In each period, on Day 4 (morning), total 16 venous blood samples will be collected
at 0.167, 0.333, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00 and 12.00 hours post-dose
Secondary Outcome
Outcome
TimePoints
Not Applicable
Not Applicable
Target Sample Size
Total Sample Size="32" Sample Size from India="32" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a Randomized, Open-Label, Two-Period, Two-Treatment,
Two-Sequence, Crossover, Multiple-Dose, Steady State, Multicenter,
Bioequivalence Study in comparison between Test product and Reference product.
Study objective is 1) To evaluate the bioequivalence of
Vigabatrin tablet USP 500 mg of Zydus Worldwide DMCC, United Arab Emirates with
Sabril® (Vigabatrin) tablet 500 mg of Lundbeck, Deerfield, IL 60015, USA in
adult subjects with refractory complex partial seizures under fasting
condition. 2) To monitor safety of
subjects.
Male or non-pregnant or non-lactating female aged between ≥ 18
to ≤ 55 years with refractory complex partial seizures will be considered for
the study. Patient will be instructed to take Oral dose of either the test
product or reference product 500 mg in the morning and evening (i.e. twice daily)
at an interval of at least 12 hours (± 30 minutes*) between the doses as per the
randomization schedule from Day 1 to Day 4 in each period.
* Note: This window period of study drug administration will
not be applicable if the subject is at
study site.