Drug-resistant Epilepsy Clinical Trial
— ARISEOfficial title:
A Randomized, Double-Blind, Placebo-Controlled, Dose Finding Study to Evaluate the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects With Drug-Resistant Epilepsy
| Verified date | December 2023 |
| Source | UCB Pharma |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of the study is to characterize the dose-response relationship with respect to efficacy of Padsevonil administered concomitantly with up to 3 anti-epileptic drugs (AEDs) for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.
| Status | Completed |
| Enrollment | 411 |
| Est. completion date | January 30, 2020 |
| Est. primary completion date | January 30, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE) criteria at least 3 years before study entry - Subject has failed to achieve seizure control with 4 tolerated and appropriately chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that were individually optimized for adequate dose and duration. Prior discontinued AED treatment would need to be assessed by the Investigator considering the patient medical records and patient and/or caregiver interview. 'Prior AED' is defined as all past and ongoing AED treatments with a start date before the Screening Visit (Visit 1) - Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic)) per month - Current treatment with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional Vagus Nerve Stimulation (VNS) or other neurostimulation treatments Exclusion Criteria: - Subject has a history of or signs of generalized or combined generalized and focal epilepsy - Cluster seizures which are uncountable in the previous 8 weeks before study entry and during 4 weeks prospective baseline - Current treatment with carbamazepine, phenytoin, primidone, phenobarbital - Current treatment/ use of (non-AED) prescription, nonprescription, dietary (eg, grapefruit or passion fruit), or herbal products that are potent inducers or inhibitors of the CYP3A4 or 2C19 pathway for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit - Subjects taking sensitive substrates of CYP2C19 for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit - Subject has been taking vigabatrin less than 2 years at study entry - Subject has been taking felbamate for less than 12 months - Subject taking retigabine for less than 4 years - Current treatment with benzodiazepines (i.e. GABA-A-ergic drugs like zolpidem, zaleplon, or zopiclone, excluding GABA-A-ergic AEDs) <3 times per week for emergencies - Subject has a current medical condition that occurred within the last 12 months which, in the opinion of the investigator, could compromise his/her safety or ability to participate in this study |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Ep0091 855 | Box Hill | |
| Australia | Ep0091 857 | Clayton | |
| Australia | Ep0091 850 | Fitzroy | |
| Australia | Ep0091 859 | Herston | |
| Australia | Ep0091 852 | Melbourne | |
| Australia | Ep0091 853 | Melbourne | |
| Australia | Ep0091 856 | Randwick | |
| Australia | Ep0091 854 | Westmead | |
| Belgium | Ep0091 102 | Brugge | |
| Belgium | Ep0091 101 | Brussels | |
| Belgium | Ep0091 105 | Gent | |
| Belgium | Ep0091 100 | Leuven | |
| Bulgaria | Ep0091 150 | Blagoevgrad | |
| Bulgaria | Ep0091 151 | Pleven | |
| Bulgaria | Ep0091 153 | Pleven | |
| Bulgaria | Ep0091 152 | Sofia | |
| Bulgaria | Ep0091 154 | Sofia | |
| Bulgaria | Ep0091 155 | Sofia | |
| Canada | Ep0091 200 | Greenfield Park | |
| Canada | Ep0091 205 | London | |
| Canada | Ep0091 201 | Montréal | |
| Czechia | Ep0091 254 | Brno | |
| Czechia | Ep0091 255 | Ostrava-Poruba | |
| Czechia | Ep0091 251 | Praha | |
| Czechia | Ep0091 252 | Praha 4 | |
| Czechia | Ep0091 250 | Praha 5 | |
| Czechia | Ep0091 253 | Praha 8 | |
| France | Ep0091 307 | Clermont-Ferrand Cedex 1 | |
| France | Ep0091 309 | Dijon | |
| France | Ep0091 300 | Lille | |
| France | Ep0091 302 | Montpellier | |
| France | Ep0091 305 | Paris | |
| France | Ep0091 303 | Rennes | |
| France | Ep0091 306 | Toulouse Cedex 9 | |
| Germany | Ep0091 361 | Bad Neustadt An Der Saale | |
| Germany | Ep0091 365 | Berlin | |
| Germany | Ep0091 362 | Bernau | |
| Germany | Ep0091 363 | Bielefeld | |
| Germany | Ep0091 358 | Bonn | |
| Germany | Ep0091 350 | Frankfurt am main | |
| Germany | Ep0091 360 | Freiburg | |
| Germany | Ep0091 364 | Hamburg | |
| Germany | Ep0091 368 | Jena | |
| Germany | Ep0091 366 | Kork | |
| Germany | Ep0091 357 | Leipzig | |
| Germany | Ep0091 353 | Marburg | |
| Germany | Ep0091 354 | München | |
| Germany | Ep0091 351 | Münster | |
| Germany | Ep0091 356 | Osnabrück | |
| Germany | Ep0091 367 | Ravensburg | |
| Germany | Ep0091 301 | Strausberg | |
| Germany | Ep0091 352 | Tübingen | |
| Hungary | Ep0091 400 | Budapest | |
| Hungary | Ep0091 403 | Budapest | |
| Hungary | Ep0091 402 | Debrecen | |
| Italy | Ep0091 462 | Bologna | |
| Italy | Ep0091 450 | Cagliari | |
| Italy | Ep0091 461 | Foggia | |
| Italy | Ep0091 452 | Milano | |
| Italy | Ep0091 459 | Pavia | |
| Italy | Ep0091 453 | Perugia | |
| Italy | Ep0091 458 | Pozzilli | |
| Italy | Ep0091 454 | Reggio Calabria | |
| Italy | Ep0091 455 | Roma | |
| Italy | Ep0091 457 | Roma | |
| Italy | Ep0091 460 | Roma | |
| Japan | Ep0091 501 | Asaka | |
| Japan | Ep0091 511 | Fukuoka | |
| Japan | Ep0091 505 | Hiroshima | |
| Japan | Ep0091 513 | Hofu | |
| Japan | Ep0091 507 | Itami | |
| Japan | Ep0091 503 | Kodaira | |
| Japan | Ep0091 514 | Kyoto | |
| Japan | Ep0091 512 | Nagakute | |
| Japan | Ep0091 510 | Niigata | |
| Japan | Ep0091 515 | Saitama | |
| Japan | Ep0091 509 | Shizuoka | |
| Lithuania | Ep0091 703 | Kaunas | |
| Lithuania | Ep0091 701 | Vilnius | |
| Lithuania | Ep0091 702 | Vilnius | |
| Mexico | Ep0091 553 | Culiacán | |
| Mexico | Ep0091 552 | Mexico Distrito Federal | |
| Poland | Ep0091 601 | Gdansk | |
| Poland | Ep0091 607 | Grodzisk Mazowiecki | |
| Poland | Ep0091 605 | Katowice | |
| Poland | Ep0091 608 | Katowice | |
| Poland | Ep0091 603 | Kraków | |
| Poland | Ep0091 604 | Lublin | |
| Poland | Ep0091 606 | Nowa Sól | |
| Poland | Ep0091 600 | Poznan | |
| Poland | Ep0091 609 | Poznan | |
| Poland | Ep0091 602 | Swidnik | |
| Portugal | Ep0091 952 | Santa Maria Da Feira | |
| Slovakia | Ep0091 004 | Bardejov | |
| Slovakia | Ep0091 001 | Hlohovec | |
| Spain | Ep0091 662 | Alicante | |
| Spain | Ep0091 651 | Barcelona | |
| Spain | Ep0091 652 | Barcelona | |
| Spain | Ep0091 658 | Barcelona | |
| Spain | Ep0091 664 | Barcelona | |
| Spain | Ep0091 668 | Bilbao | |
| Spain | Ep0091 666 | Córdoba | |
| Spain | Ep0091 650 | Madrid | |
| Spain | Ep0091 656 | Madrid | |
| Spain | Ep0091 660 | Madrid | |
| Spain | Ep0091 661 | Madrid | |
| Spain | Ep0091 659 | Málaga | |
| Spain | Ep0091 663 | Sevilla | |
| Spain | Ep0091 665 | Terrassa | |
| Spain | Ep0091 657 | Valencia | |
| Spain | Ep0091 667 | Valencia | |
| Spain | Ep0091 653 | Valladolid | |
| Turkey | Ep0091 904 | Eskisehir | |
| Turkey | Ep0091 900 | Istanbul | |
| Turkey | Ep0091 901 | Istanbul | |
| United Kingdom | Ep0091 752 | Birmingham | |
| United Kingdom | Ep0091 751 | Cardiff | |
| United Kingdom | Ep0091 756 | Inverness | |
| United Kingdom | Ep0091 757 | London | |
| United Kingdom | Ep0091 750 | Manchester | |
| United Kingdom | Ep0091 753 | Swansea | |
| United States | Ep0091 873 | Atlanta | Georgia |
| United States | Ep0091 805 | Austin | Texas |
| United States | Ep0091 844 | Austin | Texas |
| United States | Ep0091 822 | Baltimore | Maryland |
| United States | Ep0091 818 | Bethesda | Maryland |
| United States | Ep0091 839 | Chandler | Arizona |
| United States | Ep0091 838 | Cordova | Tennessee |
| United States | Ep0091 830 | Dallas | Texas |
| United States | Ep0091 836 | Dallas | Texas |
| United States | Ep0091 806 | Hackensack | New Jersey |
| United States | Ep0091 803 | Honolulu | Hawaii |
| United States | Ep0091 815 | La Jolla | California |
| United States | Ep0091 810 | Little Rock | Arkansas |
| United States | Ep0091 835 | Nashville | Tennessee |
| United States | Ep0091 827 | New York | New York |
| United States | Ep0091 809 | Ocala | Florida |
| United States | Ep0091 823 | Orlando | Florida |
| United States | Ep0091 832 | Peoria | Illinois |
| United States | Ep0091 800 | Philadelphia | Pennsylvania |
| United States | Ep0091 802 | Philadelphia | Pennsylvania |
| United States | Ep0091 825 | Port Charlotte | Florida |
| United States | Ep0091 824 | Round Rock | Texas |
| United States | Ep0091 817 | Saint Paul | Minnesota |
| United States | Ep0091 870 | San Antonio | Texas |
| United States | Ep0091 801 | San Francisco | California |
| United States | Ep0091 820 | Tallahassee | Florida |
| United States | Ep0091 845 | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| UCB Biopharma S.P.R.L. |
United States, Australia, Belgium, Bulgaria, Canada, Czechia, France, Germany, Hungary, Italy, Japan, Lithuania, Mexico, Poland, Portugal, Slovakia, Spain, Turkey, United Kingdom,
Kramer H, Bicer C, Otoul C, Rospo C, Macpherson M, Watling M, Bani M, Sciberras D, Chanteux H. Clinical Bridging Studies and Modeling Approach for Implementation of a Patient Centric Sampling Technique in Padsevonil Clinical Development. AAPS J. 2023 Nov — View Citation
Rademacher M, Toledo M, Van Paesschen W, Liow KK, Milanov IG, Esch ML, Wang N, MacPherson M, Byrnes WJ, Minh TDC, Webster E, Werhahn KJ. Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-bli — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period | During the study, participants kept diaries to record daily seizure activity. Seizure frequency refers to 28-day adjusted frequency. Seizure frequency was based on investigator assessment of participants' reports of daily seizure type and frequency. Observable focal-onset seizures refer to Type IA1, IB, and IC (ILAE Classification of Epileptic Seizures, 1981). Based on ANCOVA on change in log-transformed, 28-day adjusted seizure frequency from Baseline with treatment group as the main factor, Baseline log-transformed seizure frequency as a continuous covariate, Baseline SV2A use (yes or no) and Region (Europe, Non-Europe) as categorical factors. | From Baseline over the 12 Week Maintenance Period | |
| Primary | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject and/or Caregiver or Observed by the Investigator During the Entire Study | An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. | From Baseline until Safety Follow-Up (up to Week 23) | |
| Primary | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal | An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. | From Baseline until Safety Follow-Up (up to Week 23) | |
| Primary | Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalization or prolongation of existing hospitalization Is a congenital anomaly or birth defect Is an infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. |
From Baseline until Safety Follow-Up (up to Week 23) | |
| Secondary | 75 % Responder Rate Over the 12 Week Maintenance Period | The 75% responder rate, where a responder is a participant experiencing a =75% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period. | End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization | |
| Secondary | 50 % Responder Rate Over the 12 Week Maintenance Period | The 50% responder rate, where a responder was a participant experiencing a =50% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period. | End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization | |
| Secondary | Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period | During the study, participants kept diaries to record daily seizure activity. The percentage of participants who experienced a 50 % or greater reduction in seizure frequency per 28 days relative to Baseline (responders) was assessed. | End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT03893916 -
MEG Versus EEG HR for the Localization of the Epileptogenic Zone as Part of the Pre-surgical Assessment of Epilepsy
|
N/A | |
| Terminated |
NCT03739840 -
A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy
|
Phase 3 | |
| Terminated |
NCT03370120 -
Study to Test the Safety and Efficacy of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy
|
Phase 2 | |
| Recruiting |
NCT05769634 -
Electrophysiological Read-Out of Interoceptive Processing
|
Early Phase 1 |