Bioequivalence study of Vigabatrin Tablets 500 mg in refractory complex partial-seizure adult patients on Vigabatrin adjunctive therapy.
Completed
- Conditions
- Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures,
- Registration Number
- CTRI/2020/11/029355
- Lead Sponsor
- Amneal Pharmaceuticals LLC
- Brief Summary
A randomized, open label, multiple-dose, multi-centre,two-treatment, two-period, two-sequence, two-way crossover, steady-statepharmacokinetic bioequivalence study of Vigabatrin Tablets 500 mg manufacturedby Amneal Pharmaceuticals LLC with SABRIL (vigabatrin) tablets 500 mgManufactured by: Patheon Cincinnati, OH 45237, U.S.A. For: Lundbeck Deerfield,IL 60015, U.S.A. in refractory complex partial-seizure adult patients who arealready on established Vigabatrin adjunctive therapy under fasting conditions.
Primary Objective: To characterize steady-statepharmacokinetic profile and to assess bioequivalence of Vigabatrin Tablets 500mg manufactured by Amneal Pharmaceuticals LLC compared to SABRIL (vigabatrin)tablets 500 mg Manufactured by: Patheon Cincinnati, OH 45237, U.S.A. For:Lundbeck Deerfield, IL 60015, U.S.A. in adult patients with refractory complexpartial-seizure and who are already on established Vigabatrin adjunctivetherapy.
Secondary Objective: To monitor the safety and tolerabilityof multiple doses of Vigabatrin Tablets 500 mg in adult patients withrefractory complex partial-seizure who are already on established Vigabatrinadjunctive therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 36
Inclusion Criteria
- Patient or LAR willing and able to provide voluntary informed consent 2.
- Male or female aged 18 to 55 years (both inclusive) at the time of consent.
- Adult patients with refractory complex partial-seizure who are already on established vigabatrin adjunctive therapy with a dose of 500 mg twice daily for at least one month prior to Day 0 of the study.
- Acceptable hematology status: a.
- Hemoglobin greater than or equal to 11 g per dL b.
- Absolute neutrophil count (ANC) greater than or equal to 1500 cells per microliter c.
- Platelet count greater than or equal to 150,000 cells per microliter 5.
- Acceptable liver function: a.
- Alanine aminotransferase less than or equal to 2.5 X ULN b.
- Aspartate aminotransferase less than or equal to 2.5 X ULN c.
- Bilirubin less than 1.5 X ULN d.
- Alkaline phosphatase less than or equal to 2.5 X ULN 6.
- Patients with Creatinine clearance greater than 80 mL per minute 7.
- Only for females of child bearing potential except for those who have completed one year since menopause or have gone through hysterectomy or bilateral tubal ligation within past 6 months with negative serum pregnancy test at screening and negative urine pregnancy test on day 0.
- Women of childbearing potential, (defined as women physiologically capable of becoming pregnant, unless they are using effective method of contraception during dosing of the investigational product) practicing any two acceptable methods of contraception.
- Acceptable methods of contraception are: a.
- Oral or other (e.g. injection, patch or implant) hormonal contraception which has been used continuously for at least one month prior to the first dose of study medication b.
- Intrauterine device or intrauterine system c.
- Double barrier method of contraception condom and occlusive cap or condom and spermicidal agent d.
- Male sterilization at least 6 months prior to the screening, should be the sole male partner for that patient e.
- Female sterilization surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to study participation f.
Exclusion Criteria
- The subjects will be excluded from the study based on the following criteria: 1.
- History of hypersensitivity to Vigabatrin or to any of the excipients as judged by investigator.
- Patients who require dose-change or anticipated to have change in dose during the treatment period.
- Patient is taking other drugs associated with serious adverse ophthalmic effects, such as retinopathy.
- History of systemic illness like chronic hepatic, renal, pulmonary, cardiac disease or any other significant illness or any other significant abnormal laboratory results at the time of screening which may increase the risk to the patient, as judged by the investigator 5.
- Patient with abnormal vision assessment test at the time of screening.
- Patients with positive HIV antibody, HBsAg or HCV antibody.
- Patients who pose a significant risk of a suicide attempt based on history within the past 3 months prior to screening, investigators judgment or have answered yes on the questions 4 or 5 at Screening on Columbia Suicide Severity Rating Scale (C-SSRS) (Appendix B) 8.
- Patient with diabetic retinopathy, glaucoma or other retinal diseases.
- Patients with a decline in vision compared to baseline within 30 days prior to study enrollment 10.
- Family history of glaucoma, retinal disease, or other genetic ophthalmologic conditions 11.
- Patients who have started phenytoin, clonazepam, or drugs metabolized by CYP2C9 or had a change in the dose of these drugs less than 90 days prior to Period 01 dosing.
- Patients with progression of previously diagnosed adverse effects associated with Sabril within 30 days prior to study enrollment 13.
- Patients who are unconscious, institutionalized, or considered incompetent (e.g. severe mental illness or severe mental disability) 14.
- Concurrent exposure to medications with known or suspected retinal or optic nerve toxicity.
- A medical or surgical condition that might interfere with the absorption, metabolism or excretion of Vigabatrin.
- Patients with history of psychiatric disorders such as depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
- Alcohol or any drug dependence within past one year.
- Blood donation/loss exceeding 200 ml within 60 days prior to first day of dosing of investigational medicinal product.
- Participation in another clinical trial or use of other investigational product/ device within 60 days prior to first day of dosing of investigational medicinal product.
- Nursing mother or Lactating woman.
- Any condition/ abnormal baseline findings that in the investigators judgment might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to obtain the objective of the study e.g. low expectation of compliance to dosing or expected changes in concomitant medication that may interfere in study.
- Patient on vagal nerve stimulator as a monotherapy 23.
- Patients with presence of neurotoxicity, somnolence and fatigue, peripheral neuropathy, weight gain, edema.
- Patients with suspected signs and symptoms of COVID-19 / confirmed novel coronavirus infection (COVID-19) or with history of travel / contact with any COVID-19 positive patient/isolation/quarantine.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To characterize steady-state pharmacokinetic profile and to assess bioequivalence of Vigabatrin Tablets 500 mg manufactured by Amneal Pharmaceuticals LLC compared to SABRIL (vigabatrin) tablets 500 mg Manufactured by: Patheon Cincinnati, OH 45237, U.S.A. For: Lundbeck Deerfield, IL 60015, U.S.A. in adult patients with refractory complex partial-seizure who are already on established Vigabatrin adjunctive therapy Sample 1:Day-3&8:Pre-dose blood sample(-48.00) hrs, Sample 2:Day-4&9: Pre-dose blood sample(-24.00) hrs(Within 5 minutes prior to dosing),Sample 3to22:Day5&10: Pre-dose blood sample(00.00) hrs, 0.083 hrs, 00.17 hrs, 00.33 hrs, 00.50 hrs, 00.50 hrs, 00.75 hrs, 01.00 hrs, 01.25 hrs, 01.50 hrs, 01.75 hrs, 02.00 hrs, 02.50 hrs, 03.00 hrs, 03.50 hrs, 04.00 hrs, 05.00 hrs, 06.00 hrs, 08.00 hrs, 10.00 hrs(± 02 minutes), 12.00 hrs Within 5 minutes prior to evening dose of IP administration
- Secondary Outcome Measures
Name Time Method To monitor the safety and tolerability of multiple doses of Vigabatrin Tablets 500 mg in adult patients with refractory complex partial-seizure who are already on established Vigabatrin adjunctive therapy. Sample 1:Day-3&8:Pre-dose blood sample(-48.00) hrs, Sample 2:Day-4&9: Pre-dose blood sample(-24.00) hrs(Within 5 minutes prior to dosing),Sample 3to22:Day5&10: Pre-dose blood sample(00.00) hrs, 0.083 hrs, 00.17 hrs, 00.33 hrs, 00.50 hrs, 00.50 hrs, 00.75 hrs, 01.00 hrs, 01.25 hrs, 01.50 hrs, 01.75 hrs, 02.00 hrs, 02.50 hrs, 03.00 hrs, 03.50 hrs, 04.00 hrs, 05.00 hrs, 06.00 hrs, 08.00 hrs, 10.00 hrs(± 02 minutes), 12.00 hrs Within 5 minutes prior to evening dose of IP administration
Trial Locations
- Locations (6)
Anand Multispeciality Hospital and Research Centre
🇮🇳Gandhinagar, GUJARAT, India
Hi Tech Multispeciality Hospital
🇮🇳Gandhinagar, GUJARAT, India
Lifepoint Multispecialty Hospital
🇮🇳Pune, MAHARASHTRA, India
Medstar Specialty Hospital
🇮🇳Bangalore, KARNATAKA, India
Nirmal Hospital PVT LTD
🇮🇳Surat, GUJARAT, India
Sir Sayajirao General Hospital
🇮🇳Vadodara, GUJARAT, India
Anand Multispeciality Hospital and Research Centre🇮🇳Gandhinagar, GUJARAT, IndiaDr Rajendra AnandPrincipal investigator9824017400drrajendraanand@yahoo.com