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NCT03739840: DUET

A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy

Terminated Phase 3 Results posted Last updated 21 December 2022
What this trial tests

Phase 3 trial testing Padsevonil in Drug-Resistant Epilepsy in 232 participants. Terminated before completion.

Timeline
6 March 2019
Primary endpoint
28 September 2020
28 September 2020

Quick facts

Lead sponsorUCB Biopharma SRL
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment232
Start date6 March 2019
Primary completion28 September 2020
Estimated completion28 September 2020
Sites141 locations across Italy, Finland, Japan, Ireland, Poland, Croatia, Denmark, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

UCB Biopharma SRL — full company profile →

Who can join

18 and older, any sex, with Drug-Resistant Epilepsy or Focal-Onset Seizures. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Log-transformed Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period Primary · From Baseline over the 12 Week Maintenance Period (up to Week 16)

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 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

GroupValue95% CI
Placebo (FAS)-0.41-0.6133 – -0.2025
Padsevonil 100 mg BID (FAS)-0.35-0.54906 – -0.15705
Padsevonil 200 mg BID (FAS)-0.47-0.67559 – -0.27382
Padsevonil 400 mg BID (FAS)-0.47-0.67267 – -0.27361
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · From Baseline until Safety Follow-Up (up to Week 23)

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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

GroupValue95% CI
Placebo (SS)69.1
Padsevonil 100 mg BID (SS)83.3
Padsevonil 200 mg BID (SS)78.9
Padsevonil 400 mg BID (SS)84.7
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal Primary · From Baseline until Safety Follow-Up (up to Week 23)

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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

GroupValue95% CI
Placebo (SS)7.3
Padsevonil 100 mg BID (SS)10.0
Padsevonil 200 mg BID (SS)10.5
Padsevonil 400 mg BID (SS)20.3
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) Primary · From Baseline until Safety Follow-Up (up to Week 23)

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 as 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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or an

GroupValue95% CI
Placebo (SS)9.1
Padsevonil 100 mg BID (SS)3.3
Padsevonil 200 mg BID (SS)1.8
Padsevonil 400 mg BID (SS)10.2
75% Responder Rate From Baseline Over the 12-week Maintenance Period Secondary · From Baseline over the 12 Week Maintenance Period (up to Week 16)

The 75 % responder rate, where a responder was a participant experiencing a ≥75 % reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.

GroupValue95% CI
Placebo (FAS)13.0
Padsevonil 100 mg BID (FAS)15.3
Padsevonil 200 mg BID (FAS)12.5
Padsevonil 400 mg BID (FAS)14.3
50% Responder Rate From Baseline Over the 12-week Maintenance Period Secondary · From Baseline over the 12 Week Maintenance Period (up to Week 16)

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.

GroupValue95% CI
Placebo (FAS)27.8
Padsevonil 100 mg BID (FAS)35.6
Padsevonil 200 mg BID (FAS)33.9
Padsevonil 400 mg BID (FAS)42.9
Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period Secondary · From Baseline over the 12 Week Maintenance Period (up to Week 16)

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) were assessed.

GroupValue95% CI
Placebo (FAS)22.34± 44.56
Padsevonil 100 mg BID (FAS)11.72± 81.52
Padsevonil 200 mg BID (FAS)30.29± 39.58
Padsevonil 400 mg BID (FAS)22.41± 62.80

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAEs were collected from Baseline until Safety Follow-Up (up to Week 23). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Treatment Period (SS)
Serious: 3/55 (5%)
Deaths: 0/55
Padsevonil 100 mg BID Treatment Period (SS)
Serious: 0/60 (0%)
Deaths: 0/60
Padsevonil 200 mg BID Treatment Period (SS)
Serious: 1/57 (2%)
Deaths: 0/57
Padsevonil 400 mg BID Treatment Period (SS)
Serious: 5/59 (8%)
Deaths: 0/59
Placebo Conversion Period (SS)
Serious: 1/33 (3%)
Deaths: 0/33
Padsevonil 100 mg BID Conversion Period (SS)
Serious: 0/31 (0%)
Deaths: 0/31
Padsevonil 200 mg BID Conversion Period (SS)
Serious: 0/29 (0%)
Deaths: 0/29
Padsevonil 400 mg BID Conversion Period (SS)
Serious: 0/28 (0%)
Deaths: 0/28
Placebo Taper and SFU Period (SS)
Serious: 1/27 (4%)
Deaths: 0/27
Padsevonil 100 mg BID Taper and SFU Period (SS)
Serious: 2/30 (7%)
Deaths: 0/30
Padsevonil 200 mg BID Taper and SFU Period (SS)
Serious: 0/31 (0%)
Deaths: 0/31
Padsevonil 400 mg BID Taper and SFU Period (SS)
Serious: 1/32 (3%)
Deaths: 0/32

Serious adverse events (18 terms)

ReactionSystemPlacebo Treatment Period (…Padsevonil 100 mg BID Trea…Padsevonil 200 mg BID Trea…Padsevonil 400 mg BID Trea…Placebo Conversion Period …Padsevonil 100 mg BID Conv…Padsevonil 200 mg BID Conv…Padsevonil 400 mg BID Conv…Placebo Taper and SFU Peri…Padsevonil 100 mg BID Tape…Padsevonil 200 mg BID Tape…Padsevonil 400 mg BID Tape…
Radius fractureInjury, poisoning and procedural complications
Skin lacerationInjury, poisoning and procedural complications
Subdural haematomaInjury, poisoning and procedural complications
Wrist fractureInjury, poisoning and procedural complications
ContusionInjury, poisoning and procedural complications
Humerus fractureInjury, poisoning and procedural complications
Rib fractureInjury, poisoning and procedural complications
HyponatraemiaMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
EpilepsyNervous system disorders
Focal dyscognitive seizuresNervous system disorders
SeizureNervous system disorders
Status epilepticusNervous system disorders
AggressionPsychiatric disorders
Emotional disorderPsychiatric disorders
Suicidal ideationPsychiatric disorders
Abortion inducedSurgical and medical procedures
PneumothoraxRespiratory, thoracic and mediastinal disorders
Other adverse events (22 terms — click to expand)

ReactionSystemPlacebo Treatment Period (…Padsevonil 100 mg BID Trea…Padsevonil 200 mg BID Trea…Padsevonil 400 mg BID Trea…Placebo Conversion Period …Padsevonil 100 mg BID Conv…Padsevonil 200 mg BID Conv…Padsevonil 400 mg BID Conv…Placebo Taper and SFU Peri…Padsevonil 100 mg BID Tape…Padsevonil 200 mg BID Tape…Padsevonil 400 mg BID Tape…
SomnolenceNervous system disorders
DizzinessNervous system disorders
FatigueGeneral disorders
HeadacheNervous system disorders
AstheniaGeneral disorders
Memory impairmentNervous system disorders
Disturbance in attentionNervous system disorders
DysarthriaNervous system disorders
InsomniaPsychiatric disorders
Gait disturbanceGeneral disorders
NasopharyngitisInfections and infestations
TremorNervous system disorders
SeizureNervous system disorders
IrritabilityPsychiatric disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FallInjury, poisoning and procedural complications
ContusionInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
Balance disorderNervous system disorders
AnxietyPsychiatric disorders
HypotensionVascular disorders

Most-reported serious reactions: Radius fracture, Skin laceration, Subdural haematoma, Wrist fracture, Contusion, Humerus fracture, Rib fracture, Hyponatraemia.

Data from ClinicalTrials.gov NCT03739840 adverse events section.

Sponsor's own description

The purpose of the study is to evaluate the efficacy, safety and tolerability of the 3 selected dose regimens of padsevonil (PSL) administered concomitantly with up to 3 anti-epileptic drugs (AEDs) compared with placebo for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials.
    Rademacher M, Toledo M, Van Paesschen W, Liow KK, et al · · 2022 · cited 17× · PMID 36176044 · DOI 10.1002/epi4.12656
  2. SV2B Promotes the Progression of TFE3-Rearranged Renal Cell Carcinoma by Interacting with HERC2 to Impede the Degradation of NF-κB Subunits.
    Feng H, Xiong Z, Yu S, Liu J, et al · · 2026 · cited 1× · PMID 41199339 · DOI 10.1002/advs.202509443
  3. The Complexity and Challenges of Developing Effective Epilepsy Therapies: Lessons to be Learned from Comparing Cenobamate, Carisbamate, and Padsevonil.
    Löscher W, White HS, Klein P. · · 2026 · PMID 41915362 · DOI 10.1007/s40263-026-01284-x

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