an open-label extension study of ucb0942 in adult patients with highly drug-resistant focal epilepsy

Conditions: Highly Drug-resistant Focal Epilepsy

Summary: the purpose of study ep0073 is to assess the long-term safety, tolerability, and efficacy during 5 years of treatment with the drug ucb0942 in patients with highly drug-resistant focal epilepsy. also, the effects of ucb0942 on the patient's quality of life will be explored.

for those subjects who benefit substantially from ucb0942 in the multicenter, randomized, double-blind, placebo-controlled, parallel group study ep0069, the current open-label extension study ep0073 will provide an opportunity to continue ucb0942 treatment after a careful evaluation of the individual benefit-risk balance and with close monitoring of safety, tolerability and efficacy of long-term study treatment.

Eligibility criteria:
inclusion criteria: * a written informed consent form approved by the independent ethics committee is signed and dated by the subject, after the investigator assesses whether the subject is able to understand the potential risks and benefits of participating in the study * subject must have completed visit 13 (v13) of the outpatient maintenance period of ep0069 to be eligible for enrollment into ep0073 * in ep0069, the subject demonstrated a reduction in frequency and/or severity of seizures as compared to baseline that is considered clinically significant by the investigator and significant by the subject * in ep0069, the subject experiences substantial benefit from ucb0942 with acceptable tolerability according to the subject and investigator * no tolerability issues that can outweigh attained benefits, in the opinion of the investigator * female subjects of nonchildbearing potential (premenarcheal, postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, and complete hysterectomy) are eligible. female subjects of childbearing potential are eligible if they use medically accepted contraceptive methods * male subject confirms that, during the study period and for a period of 3 months after the final dose, when having sexual intercourse with a woman of childbearing potential, he will use a barrier contraceptive (eg, condom)exclusion criteria: * subject has active suicidal ideation as indicated by a positive response ('yes') to either question 4 or question 5 of the 'since last visit' version of the columbia suicide severity rating scale. the subject should be referred immediately to a mental healthcare professional and must be withdrawn from the study * subject has taken other (non-anti-epileptic drug) prescription, non-prescription, dietary (eg, grapefruit or passion fruit), or herbal products that are potent inducers or inhibitors of the cyp3a4 pathway for 2 weeks (or 5 half lives whichever is longer) prior to study entry * subject has an abnormality in the 12-lead electrocardiography that, in the opinion of the investigator, increases the risks associated with participating in the study. in addition, any subject with any of the following findings will be excluded: 1. prolonged qtc (bazett's, machine-read) interval defined as \> 450 ms for males and \> 470 ms for females 2. bundle branch blocks and other conduction abnormalities other than mild first degree atrioventricular block (defined as pr interval \>= 220 ms) 3. irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats 4. in the judgment of the investigator, t-wave configurations are not of sufficient quality for assessing qt interval duration * subject has a clinically significant abnormality on echocardiography at the entry visit (v2) of ep0073 * upper limit of normal (uln) of any of the following: alanine aminotransferase (alt), aspartate aminotransferase (ast), alkaline phosphatase (alp), or \>uln total bilirubin (\>=1.5xuln total bilirubin if known gilbert's syndrome) at the ev (v2) of ep0073 (v15 of ep0069). if subject has elevations only in total bilirubin that are \>uln and \<1.5xuln, fractionate bilirubin to identify possible undiagnosed gilbert's syndrome (ie, direct bilirubin \<35%). for enrolled subjects with a baseline result * uln for alt, ast, alp, or total bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic case report form (ecrf). if subject has \>uln alt, ast, or alp that does not meet the exclusion limit at screening (ie, the value is * uln but \<=2xuln at the ev \[v2\] of ep0073), repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. in case of a clinically relevant increase, inclusion of the subject must be discussed with the medical monitor

Keywords: drug-resistance focal epilepsy partial-onset seizures