Clinical trial NCT02625090: An Open-label Extension Study of UCB0942 in Adult Patients With Highly Drug-resistant Focal Epilepsy
Official title: An Open-label, Multicenter, Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of UCB0942 When Used as Adjunctive Therapy for Partial-onset Seizures in Adult Subjects With Highly Drug-resistant Focal Epilepsy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Highly Drug-resistant Focal Epilepsy
Keywords: Drug-resistance
focal epilepsy
partial-onset seizures
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2015-12-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE) From the Beginning at Entry Visit (EV) of the Evaluation Period to End of Safety Follow-Up Visit During the EP0073 Study
timeFrame: From Entry Visit to End of Safety Follow-Up Visit (up to 5 years)
measure: 75% Responder Rate by 3-month Interval (Month 0 to 3) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month 0-3)
measure: 75% Responder Rate by 3-month Interval (Month >3-6) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >3-6)
measure: 75% Responder Rate by 3-month Interval (Month >6-9) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >6-9)
measure: 75% Responder Rate by 3-month Interval (Month >9-12) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >9-12)
measure: 75% Responder Rate by 3-month Interval (Month >12-15) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >12-15)
measure: 75% Responder Rate by 3-month Interval (Month >15-18) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >15-18)
measure: 75% Responder Rate by 3-month Interval (Month >18-21) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >18-21)
measure: 75% Responder Rate by 3-month Interval (Month >21-24) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >21-24)
measure: 75% Responder Rate by 3-month Interval (Month >24-27) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >24-27)
measure: 75% Responder Rate by 3-month Interval (Month >27-30) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >27-30)
measure: 75% Responder Rate by 3-month Interval (Month >30-33) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >30-33)
measure: 75% Responder Rate by 3-month Interval (Month >33-36) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >33-36)
measure: 75% Responder Rate by 3-month Interval (Month >36-39) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >36-39)
measure: 75% Responder Rate by 3-month Interval (Month >39-42) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >39-42)
measure: 75% Responder Rate by 3-month Interval (Month >42-45) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >42-45)
measure: 75% Responder Rate by 3-month Interval (Month >45-48) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >45-48)
measure: 75% Responder Rate by 3-month Interval (Month >48-51) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >48-51)
measure: 75% Responder Rate by 3-month Interval (Month >51-54) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >51-54)
measure: 75% Responder Rate by 3-month Interval (Month >54-57) Over the Evaluation Period
timeFrame: Over 3-month interval over the Evaluation Period (Month >54-57)
Secondary outcomes:
measure: Median Partial-onset Seizure Frequency Per 28 Days by 3-month Intervals Over the Evaluation Period of the EP0073 Study
timeFrame: Over the 3-month interval: Month 0-3, >3-6, >6-9, >9-12, >12-15, >15-18, >18-21, >21-24, >24-27, >27-30, >30-33, >33-36, >36-39, >39-42, >42-45, >45-48, >48-51, >51-54, >54-57 over the Evaluation Period
measure: Median Partial-onset Seizure Frequency Per 28 Days by Seizure Type by 3-month Intervals Over the Evaluation Period of the EP0073 Study
timeFrame: Over the 3-month interval: Month 0-3, >3-6, >6-9, >9-12, >12-15, >15-18, >18-21, >21-24, >24-27, >27-30, >30-33, >33-36, >36-39, >39-42, >42-45, >45-48, >48-51, >51-54, >54-57 over the Evaluation Period
measure: Percent Change in Partial-onset Seizure Frequency Relative to the Baseline Period Defined in EP0069 by 3-month Intervals Over the Evaluation Period of the EP0073 Study
timeFrame: Over the 3-month interval: Month 0-3, >3-6, >6-9, >9-12, >12-15, >15-18, >18-21, >21-24, >24-27, >27-30, >30-33, >33-36, >36-39, >39-42, >42-45, >45-48, >48-51, >51-54, >54-57 over the Evaluation Period, Relative to Baseline (of EP0069)
measure: 50% Responder Rate by 3-month Intervals Over the Evaluation Period of the EP0073 Study
timeFrame: Over the 3-month interval: Month 0-3, >3-6, >6-9, >9-12, >12-15, >15-18, >18-21, >21-24, >24-27, >27-30, >30-33, >33-36, >36-39, >39-42, >42-45, >45-48, >48-51, >51-54, >54-57 over the Evaluation Period
measure: Percentage of Seizure-free Days by 3-month Intervals Over the Evaluation Period
timeFrame: Over the 3-month interval: Month 0-3, >3-6, >6-9, >9-12, >12-15, >15-18, >18-21, >21-24, >24-27, >27-30, >30-33, >33-36, >36-39, >39-42, >42-45, >45-48, >48-51, >51-54, >54-57 over the Evaluation Period
measure: Seizure-free Rate Over the Evaluation Period
timeFrame: Over the Evaluation Period (up to 5 years)
measure: Changes in Quality of Life in Epilepsy 31-P (QOLIE-31-P) Total Score From Visit 3 (Week 2) of EP0069 Through the Assessment of the Evaluation Period of EP0073
timeFrame: Month 3, 7, 13, 19, 25, 31, 37, 43, 49, early discontinuation visit (EDV) (up to Month 58), Relative to Baseline (of EP0069)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Ep0073 103
city: Ghent
country: Belgium
facility: Ep0073 101
city: Leuven
country: Belgium
facility: Ep0073 102
city: Sofia
country: Bulgaria
facility: Ep0073 201
city: Bielefeld
country: Germany
facility: Ep0073 402
city: Radeberg
country: Germany
facility: Ep0073 403
city: Ravensburg
country: Germany
facility: Ep0073 405
city: Budapest
country: Hungary
facility: Ep0073 601
city: Budapest
country: Hungary
facility: Ep0073 602
city: Heeze
country: Netherlands
facility: Ep0073 302
city: Barcelona
country: Spain
facility: Ep0073 502
city: L'Hospitalet de Llobregat
country: Spain
facility: Ep0073 505
city: Madrid
country: Spain
facility: Ep0073 506
city: Sevilla
country: Spain
facility: Ep0073 501
city: Valencia
country: Spain
facility: Ep0073 503
Study officials:
affiliation: +1 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: