A Single Dose, Randomized, Open-label, Two-way Crossover Bioequivalence Study of Generic Levetiracetam 500 mg Film-coated Tablets and Reference Product (Keppra) in Healthy Thai Volunteers under Fasting Conditions

Not Applicable

• Conditions: 1.Healthy Thai male or female subjects between the ages of 18 to 55 years.2.Body mass index between 18.0 to 30.0 kg/m2.3.Normal laboratory values, including vital signs and physical examination; healthy

• Registration Number: TCTR20190131005
• Lead Sponsor: Internnational Bio Service CO.,LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-31
• Study Completion: 2019-05-24
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Pending (Not yet recruiting)
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

1.Healthy Thai male or female subjects between the ages of 18 to 55 years.
2.Body mass index between 18.0 to 30.0 kg/m2.
3.Normal laboratory values, including vital signs and physical examination, for all parameters in clinical laboratory tests at screening.
Any abnormalities from the normal or reference range will be carefully considered clinically relevant by the physician as individual cases, documented in study files prior to enrolling the subject in this study.
4.Non-pregnant woman (negative pregnancy test) and not currently breast feeding.
5.Female subjects abstain from either hormonal methods of contraception (including oral or transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs, postcoital contraceptive methods) or hormone replacement therapy for at least 28 days prior to admission in Period 1. Injectable contraceptives e.g. Depo-Provera® will be discontinued at least 6 months prior to admission in Period 1. Subjects agree to use acceptable non-hormonal contraceptive methods such as condom, diaphragm, foams, jellies, or abstinence for at least 14 days prior to admission in Period 1 until 7 days after the end of study in Period 2. Female subjects of non-childbearing potential must meet at least one of the following criteria prior to admission in Period 1:
Postmenopausal for at least 1 year or
Surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) at least 6 months
6.Male subjects who are willing or able to use effective contraceptive e.g. condom or abstinence after admission in Period 1 until 7 days after the end of study in Period 2.
7.Have voluntarily given written informed consent (signed and dated) by the subject prior to participating in this study.

Exclusion Criteria

1.History of allergic reaction or hypersensitivity to levetiracetam or other pyrrolidone derivatives or any of the excipients
2.History or evidence of clinically significant renal, hepatic, gastrointestinal, hematological (e.g. anemia), endocrine (e.g. thyroid), pulmonary or respiratory (e.g. asthma), cardiovascular, psychiatric, neurologic (e.g. convulsion), allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or any significant ongoing chronic medical illness
3.History or evidence of decreased blood cell counts e.g. neutropenia, agranulocytosis, leucopenia, thrombocytopenia or pancytopenia. This event might be affected the safety of subject as judged by the physician.
4.History or evidence of behavioral abnormalities e.g. psychotic symptoms, irritability, aggressive behavior or depress
5.History of suicidal thoughts, behavior or suicide attempts in the past 30 days prior to screening or during enrollment in the study
6.History of problems with swallowing tablet or capsule
7.History of sensitivity to heparin or heparin-induced thrombocytopenia
8.Any condition possibly affecting drug absorption e.g. gastrectomy, enterectomy, gastritis or duodenal or gastric ulceration other than appendectomy
9.History of preceding diarrhea within 24 hours prior to admission in each period
10.History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse (morphine, marijuana or methamphetamine)
11.12-lead ECG demonstrating QTc >450 msec, a QRS interval >120 msec or with an abnormality considered clinically significant at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG will be repeated two more times and the average of the three QTc or QRS values will be used to determine the subject’s eligibility.
12.Investigation with blood sample shows positive test for HBsAg.
13.Abnormal liver function, ≥ 1.5 times of upper normal limit of reference range for ALT, AST or bilirubin levels at screening laboratory test
14.History or evidence of habitual use of tobacco or nicotine containing products and cannot abstain for at least 7 days prior to admission and continued until last pharmacokinetic blood sample collection in each study period
15.History or evidence of alcoholism, regular alcohol consumption or alcohol-containing products and cannot abstain for at least 7 days prior to admission and continued until last pharmacokinetic blood sample collection in each study period
16.History or evidence of habitual consume of tea, coffee, xanthine or caffeine containing products and cannot abstain for at least 7 days prior to admission and continued until last pharmacokinetic blood sample collection in each study period
17.Consume or drink juice of grapefruit or orange or pomelo or its supplement/containing products and cannot abstain for at least 7 days prior to admission and continued until last pharmacokinetic blood sample collection in each study period
18.Use of prescription or nonprescription drugs (e.g. paracetamol, erythromycin, ketoconazole, antacid, laxatives), herbal medications or supplements (e.g. St. John's wort), vitamins or mineral (e.g. iron) or dietary supplements within 14 days prior to admission in Period 1 or during enrollment
1

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine and compare the rate and extent of absorption T0-36 hrs., N = 26 (24+2), sampling point Cmax, AUC0-tlast, and AUC0-∞

Secondary Outcome Measures

Name	Time	Method
To evaluate safety of test and reference formulations T0-36 hrs., N = 26 (24+2), sampling point Tmax, t1/2, AUC0-tlast/AUC0-∞, AUC%extrapolate,λz, and MRT