A Phase 3 interventional study of USL261 in Epilepsy, sponsored by UCB Biopharma S.P.R.L.. Terminated at 58 sites in 10 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2023-01-20.
Sponsored by UCB Biopharma S.P.R.L. (part of UCB S.A.) · Phase 3, Interventional, and Treatment
The purpose of this study is to examine the long-term safety and tolerability of USL261 in the treatment of seizure clusters.
Participants who completed study P261-401 (NCT01390220), a randomized double-blind study of USL261 (intranasal midazolam) versus placebo to acutely treat a seizure cluster episode, were eligible to to enroll in this open-label extension study (P261-402). The participant's caregiver administered a USL261 5 milligram (mg) dose for a seizure episode meeting study criteria. A second USL261 5 mg dose could be administered after 10 minutes and up to 6 hours after the first dose for persistent or recurrent seizures, unless the participant met exclusions to administration of the second dose. A participant could have more than 1 seizure cluster episode treated during his/her study participation.
1,848 studies on the registry are indexed under Epilepsy; 422 are open to participants now.
This study's enrollment of 175 is above the median of 50 across 1,239 interventional studies indexed under Epilepsy.
Browse Epilepsy studies →UCB Biopharma S.P.R.L. is the lead sponsor of 48 studies on the registry; none are open to participants now.
Of its 15 completed or terminated interventional studies of FDA-regulated products, 12 (80%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intranasal midazolam 5 mg
Drug: USL261
Duration of Safety Observation
Duration of participant study participation for collection of long term safety data
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants Meeting Predefined Safety Criteria for Vital Signs
Participants meeting predefined safety criteria for vital signs (systolic blood pressure \[SBP\] \<85 mm Hg, SBP change from baseline \>/= 40 mm Hg, diastolic BP \[DBP\] \<50 mm Hg, DBP change from baseline \>/=30 mm Hg, pulse rate \<50 beats per minute (bpm), pulse rate \>120 bpm, pulse rate change \>/= 40 bpm at any visit post baseline or for caregiver recorded participant respiration rate \[RR\] \<8 breaths per minute (brpm) or \>24 brpm) after any USL261 treated seizure cluster episode. Abnormal vital signs were assessed separately by investigator and recorded as adverse events if applicable.
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Laboratory Abnormalities Meeting Predefined Criteria
Participants with abnormal laboratory finding, at any time post baseline, meeting predefined criteria. Abnormal laboratory findings were assessed separately by investigator and recorded as adverse events if applicable. Alanine aminotransferase (ALT); Alkaline phosphatase (ALP); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); upper limit of normal (ULN)
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Clinically Significant Abnormalities Physical Examination
Participants with abnormal findings, at any time post baseline, on physical examination considered clinically significant by the investigator.
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Clinically Significant Abnormalities on Neurologic Examination
Participants with abnormal findings, at any time post baseline, on neurologic examination considered clinically significant by the investigator
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Clinically Significant Abnormalities on Nasal Examination
Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participant Change in B-SIT Score
Change in participant Brief Smell Identification Test (B-SIT) score from baseline to last visit with assessment. The B-SIT is a self-administered 12-item test; the score indicates odors correctly identified (0 to 12). The B-SIT was added while the study was already ongoing (Protocol Amendment 4, 20 May 2015) in response to a regulatory request. The test was only implemented at sites in the United States and included only participants considered by the investigator to have adequate cognitive ability to perform the test. Baseline was defined as the latest non-missing value prior to administration of USL261 in the Test Dose Phase of Study P261-401.
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Suicidal Ideation
Participants with suicidal ideation reported on Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at any post-baseline visit. Responses including: Wish to be Dead; Non-Specific Active Suicidal Thoughts; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent; and Any Suicidal Ideation Regardless of Type.
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Emergency Room/Emergency Medical Service Visits
Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)
Time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success: Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after administration of first dose of USL261 (intranasal midazolam 5 mg)
Time frame: 6 hours after first dose of USL261 for each treated seizure cluster
| Milestone | USL261 |
|---|---|
| Started | 175 |
| Exposed | 161 |
| Completed | 1 |
| Not completed | 174 |
| Withdrew: Discontinued prior to study treatment | 14 |
| Withdrew: Site closure | 62 |
| Withdrew: Study termination | 29 |
| Withdrew: Withdrawal by subject | 25 |
| Withdrew: No treated scs within protocol window | 13 |
| Withdrew: Noncompliance | 8 |
| Withdrew: Caregiver no longer available | 7 |
| Withdrew: Adverse event | 4 |
| Withdrew: Protocol violation | 4 |
| Withdrew: Lack of efficacy | 4 |
| Withdrew: Investigator no longer available | 2 |
| Withdrew: Study drug not available | 2 |
Duration of participant study participation for collection of long term safety data
| months | USL261 |
|---|---|
| Duration of Safety Observation | 16.80 (1.0 to 55.7) |
Participants meeting predefined safety criteria for vital signs (systolic blood pressure \[SBP\] \<85 mm Hg, SBP change from baseline \>/= 40 mm Hg, diastolic BP \[DBP\] \<50 mm Hg, DBP change from baseline \>/=30 mm Hg, pulse rate \<50 beats per minute (bpm), pulse rate \>120 bpm, pulse rate change \>/= 40 bpm at any visit post baseline or for caregiver recorded participant respiration rate \[RR\] \<8 breaths per minute (brpm) or \>24 brpm) after any USL261 treated seizure cluster episode. Abnormal vital signs were assessed separately by investigator and recorded as adverse events if applicable.
| Participants | USL261 |
|---|---|
| SBP <85 mm Hg | 0 |
| SBP change from baseline ≥ 40 mm Hg | 1 |
| DBP <50 mm Hg | 2 |
| DBP change from baseline ≥ 30 mm Hg | 3 |
| Pulse rate <50 bpm | 2 |
| Pulse rate >120 bpm | 1 |
| Pulse rate change from baseline >/= 40 bpm | 4 |
| Caregiver recorded RR <8 brpm | 1 |
| Caregiver recorded RR >24 brpm | 29 |
Participants with abnormal laboratory finding, at any time post baseline, meeting predefined criteria. Abnormal laboratory findings were assessed separately by investigator and recorded as adverse events if applicable. Alanine aminotransferase (ALT); Alkaline phosphatase (ALP); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); upper limit of normal (ULN)
| Participants | USL261 |
|---|---|
| ALT >ULN & ≤3xULN | 26 |
| Albumin <30 g/L | 2 |
| ALP >2.5xULN | 1 |
| AST >ULN & ≤3xULN | 17 |
| AST >5x ULN & <20xULN | 1 |
| Bicarbonate <15.9 mmol/L | 6 |
| Cholesterol >7.75 mmol/L | 5 |
| Creatinine >1.5xULN | 1 |
| Creatinine >2x baseline | 2 |
| GGT >2.5xULN | 14 |
| Glucose <3 mmol/L | 3 |
| Glucose <8.9 mmol/L | 5 |
| Phosphate <0.8 mmol/L | 13 |
| Potassium >5.5 mmol/L | 5 |
| Sodium <130 mmol/L | 11 |
| Sodium >150 mmol/L | 1 |
| Hemoglobin <100 g/L | 5 |
| Hemoglobin decrease 20 g/L | 10 |
| Leukocytes <3x10^9/L | 4 |
| Lymphocytes <0.8x10^9/L | 4 |
| Neutrophils <1.5x10^9/L | 8 |
Participants with abnormal findings, at any time post baseline, on physical examination considered clinically significant by the investigator.
| Participants | USL261 |
|---|---|
| Skin | 2 |
| Head/Eyes/Ears/Nose/Throat | 0 |
| Neck | 1 |
| Thyroid | 0 |
| Lungs | 0 |
| Heart | 0 |
| Abdomen | 0 |
| Lymph nodes | 0 |
| Extremities | 0 |
Participants with abnormal findings, at any time post baseline, on neurologic examination considered clinically significant by the investigator
| Participants | USL261 |
|---|---|
| Mental status | 10 |
| Cranial nerves II-XII | 1 |
| Motor strength of limbs | 2 |
| Deep tendon reflexes | 2 |
| Sensory exam | 1 |
| Station and gait | 5 |
| Hopping | 0 |
| Romberg test | 0 |
| Finger-to-nose test | 1 |
| Heel-to-shin test | 1 |
| Rapid alternating movements | 2 |
| Nystagmus | 0 |
| Tremor/Other abnormal movements | 0 |
Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator
| Participants | USL261 |
|---|---|
| Participants With Clinically Significant Abnormalities on Nasal Examination | 1 |
Change in participant Brief Smell Identification Test (B-SIT) score from baseline to last visit with assessment. The B-SIT is a self-administered 12-item test; the score indicates odors correctly identified (0 to 12). The B-SIT was added while the study was already ongoing (Protocol Amendment 4, 20 May 2015) in response to a regulatory request. The test was only implemented at sites in the United States and included only participants considered by the investigator to have adequate cognitive ability to perform the test. Baseline was defined as the latest non-missing value prior to administration of USL261 in the Test Dose Phase of Study P261-401.
| score on a scale | USL261 |
|---|---|
| Participant Change in B-SIT Score | -0.6 ± 1.2 |
Participants with suicidal ideation reported on Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at any post-baseline visit. Responses including: Wish to be Dead; Non-Specific Active Suicidal Thoughts; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent; and Any Suicidal Ideation Regardless of Type.
| Participants | USL261 |
|---|---|
| Wish to be dead | 3 |
| Non-specific active | 3 |
| Active without specific plan | 3 |
| Active with specific plan/intent | 1 |
| Any suicidal ideation | 4 |
Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)
| Participants | USL261 |
|---|---|
| Emergency Room/Emergency Medical Service Visits | 20 |
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success: Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after administration of first dose of USL261 (intranasal midazolam 5 mg)
| Seizure cluster episodes | USL261 |
|---|---|
| Number of Treated Seizure Clusters Meeting Criteria for Treatment Success | 1108 |
Collected over Original protocol - each participant 2 years from enrollment; Amended protocol - each participant open-ended from enrollment (up to 4 years or longer as approved by Health Authority where study being conducted). Actual individual participant duration 1.0 to 55.7 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| USL261 | 0/161 (0%) | 8/161 (5%) | 33/161 (20.5%) |
| Event | USL261 |
|---|---|
| Seizure clusterNervous system disorders | 2/161 |
| ConvulsionNervous system disorders | 2/161 |
| Status epilepticusNervous system disorders | 2/161 |
| EpilepsyNervous system disorders | 1/161 |
| NauseaGastrointestinal disorders | 1/161 |
| PyrexiaGeneral disorders | 1/161 |
| Blood pressure increasedInvestigations | 1/161 |
| Event | USL261 |
|---|---|
| Nasal discomfortRespiratory, thoracic and mediastinal disorders | 20/161 |
| SomnolenceNervous system disorders | 15/161 |
| HeadacheNervous system disorders | 10/161 |
Participants exposed to at least 1 dose of USL261
| Age, Categorical(Participants) | USL261 |
|---|---|
| <=18 years | 8 |
| Between 18 and 65 years | 153 |
| >=65 years | 0 |
| Age, Continuous(years) | USL261 |
|---|---|
| Mean | 32.9 ± 11.96 |
| Sex: Female, Male(Participants) | USL261 |
|---|---|
| Female | 80 |
| Male | 81 |
| Ethnicity (NIH/OMB)(Participants) | USL261 |
|---|---|
| Hispanic or Latino | 8 |
| Not Hispanic or Latino | 153 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | USL261 |
|---|---|
| American Indian or Alaska Native | 2 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 4 |
| White | 152 |
| More than one race | 0 |
| Unknown or Not Reported | 2 |
| Region of Enrollment(participants) | USL261 |
|---|---|
| Canada | 1 |
| Hungary | 10 |
| United States | 56 |
| Ukraine | 53 |
| Poland | 12 |
| Israel | 5 |
| Australia | 12 |
| Germany | 7 |
| Spain | 5 |
| Body Mass Index(kg/m˄2) | USL261 |
|---|---|
| Median | 24.7 (17.7 to 43.0) |
| Seizure cluster episodes in year before Visit 1 in Study P261-401(seizure cluster episodes) | USL261 |
|---|---|
| Median | 18.0 (3 to 999) |
3 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Jul 2012 to primary completion in Apr 2017, 57 months.
Results were first posted in Jun 2019, 2 years 2 months after primary completion. A results delay was requested in Mar 2018.
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This study is terminated, as verified in Jan 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Midazolam