A clinical trial of two products Vigabatrin 500 mg tablets compared to SABRIL(Vigabatrin) Tablets 500mg to study the pharmacokinetics and safety in adult refractory complex partial-seizure patientâ??s who are already on stable dose of Vigabatrin.
- Conditions
- Health Condition 1: G402- Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures
- Registration Number
- CTRI/2020/08/027254
- Lead Sponsor
- Aucta Pharmaceuticals Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 24
Prior to Stabilization (Day -36):
1.Availability for the entire study
2.Male or female patients
3.Patient aged of at least 18 years but not older than 65 years.
4.The patient has refractory Complex Partial Seizure/ focal epilepsy as evidenced by the attainment of all the following criteria:
a.The patient has failed because of lack of efficacy with 2 or more anti-epileptic drugs (AEDs) of differing pharmacologic mechanisms administered as monotherapy or polytherapy at the therapeutic dose
b.The patient should be taking at least 1 AED (A vagal nerve stimulator is not counted as an AED)
5.Patients must agree not to change their use of prescription medication(s) or over-the-counter (OTC) medicines (including natural food supplements and vitamins) within 30 days prior to administration of study drug or during the study unless dose adjustment are needed for the safety of the patients in which case the participation in the study will be re-evaluate on the case-by-case basis.
6.Patients with clinically non-significant findings on ophthalmologic assessments for visual field and visual acuity.
7.Patients with adequate hematopoeitic and liver function, defined as:
•Hemoglobin of >= 9.0 g/dL
•ANC >= 1500/mm3, Platelet count >= 100,000/mm3
•AST and ALT <= 3 times ULN, Alkaline phosphatase <= 2.5 times ULN, Bilirubin <= 1.5 times ULN
8.Patient or his/her Legally Acceptable Representative willing to adhere to the protocol requirements as evidenced by ICF duly read, signed and dated.
9.Motivated patient and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee.
10.Female patient of childbearing potential must have a negative serum pregnancy test.
11.Women of childbearing potential must agree to use adequate contraception prior to study entry, and for 60 days following completion of therapy.
12.Females must use acceptable and effective methods of contraception such as the following:
• Tubal sterilization (tubal ligation performed more than one month before Study Day 1; transcervical tubal occlusion procedure performed more than six months before Study Day 1) or
• Intrauterine Device (IUD) or
• Progestin Implant (i.e. Implanon or its equivalent) or
• Progestin injection or progestin oral contraceptive pill + one barrier method (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom) or
• Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom) or
• Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner)
13.Male subjects agreed to use contraceptive methods prior to study entry, and for 60 days following completion of study.
At the time of Screening Period and/ or Randomization Day (Day -7 to Day 0):
1.Patient receiving twice daily doses of Vigabatrin 500 mg for over at least 28 days before the 1st drug administration of the study.
2.Patient/ LAR must be willing for switch from the
Prior to Stabilization (Day -36):
1.History or presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease with the exception of the illness or refractory complex partial seizures/ focal seizures and conditions associated with refractory complex partial seizures/ focal seizures.
2.Pre-existing ocular or neurological disease that might affect bilateral visual fields or interfere with perimetry (e.g., aphakia, visually significant cataract, glaucoma, diabetic retinopathy, ischemic optic neuropathy, multiple sclerosis).
3.Clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination (ECG, vital signs) other than the illness and conditions associated with refractory complex partial seizures/ focal epilepsy.
4.Concurrent exposure to medications with known or suspected retinal or optic nerve toxicity.
5.Suicidality state or suicidal behavior as per the C-SSRS baseline-screening.
6.Presence of observed abnormality that would be clinically significant in the opinion of the Investigator
7.Use of drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma.
8.Significant history of drug dependency or alcohol abuse ( > 3 units of alcohol per day, intake of excessive alcohol, acute or chronic).
9.Concurrent use of the ketogenic or similar diet.
10.Patient on vagal nerve stimulator as a monotherapy.
11.Patients with emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
12.Patient had received any investigational drug within the past 90 days.
13.Patient had history of difficulty with donating blood or difficulty in accessibility of veins.
14.Patients with Peripheral Neuropathy.
15.Patient who are pregnant or nursing females.
16.Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb).
17.Patient at high risk of ophthalmic abnormalities and other types or irreversible vision loss as per clinical symptoms or results of the visual examination in the opinion of an ophthalmologist at screening. (Visual examination will include 1) visual acuity test with their usual glasses/contact lenses or have undergone refractive surgery and 2) standardized static perimetry test 30-2 [Humphrey/Octopus or Goldman]).
18.Patient presenting visual field defects based clinical symptoms or based on the results of the visual examination in the opinion of an ophthalmologist that could lead to ophthalmologic abnormalities.
19.Donation of 500 mL or more of blood (blood donor center, clinical studies, etc.) in the previous 56 days before day 1 of this study.
At the time of Screening Period and/ or Randomization Day (Day -7 to Day 0):
1.History of significant hypersensitivity to vigabatrin or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
2.Suicidality state or suicidal behavior as per the C-SSRS screening.
3.Presence of observed abnormality that would be clinically significant in the opinion of the Investigator
4.Patients with history of allergic reactions to Vigabatrin.
5.Patients with emergence or worsening of d
Study & Design
- Study Type
- BA/BE
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Area under the plasma concentration â?? time curve over the steady state dosing interval <br/ ><br>2. Maximum concentration over the steady state dosing intervalTimepoint: pre-dose blood samples collected on Day 3, 4 and 5 in Period I and on Day 8, 9 and 10 in Period II. Post dose samples 0.17, 0.33, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75,2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.00 and 12.00 hours post morning dose on Day 5 and Day 10
- Secondary Outcome Measures
Name Time Method