Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2011-004109-25
    Sponsor's Protocol Code Number:P261-402
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2012-06-14
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2011-004109-25
    A.3Full title of the trial
    An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects with Seizure Clusters
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects with Seizure Clusters
    A.4.1Sponsor's protocol code numberP261-402
    A.5.4Other Identifiers
    Name:US IND Number Number:77,421
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUpsher-Smith Laboratories, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportUpsher-Smith Laboratories, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationinVentiv Health Clinical UK Limited
    B.5.2Functional name of contact pointRegulatory Operations
    B.5.3 Address:
    B.5.3.1Street AddressThames House, 17-19, Marlow Road
    B.5.3.2Town/ cityMaidenhead, Berkshire
    B.5.3.3Post codeSL6 7AA
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 1628587430
    B.5.5Fax number+441628408428
    B.5.6E-mailRegOpsEurope@inventivhealth.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIntranasal midazolam
    D.3.2Product code USL261
    D.3.4Pharmaceutical form Nasal spray, solution in single-dose container
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntranasal use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMIDAZOLAM
    D.3.9.1CAS number 59467-70-8
    D.3.9.2Current sponsor codeUSL261
    D.3.9.4EV Substance CodeSUB08950MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Epilepsy
    E.1.1.1Medical condition in easily understood language
    Epilepsy
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10015052
    E.1.2Term Epileptic seizure
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the long-term safety and tolerability of USL-261 in the treatment of seizure clusters using the following assessments:
    • Caregiver-recorded respiration rate at 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours after study drug administration.
    • Adverse events (AEs).
    • Clinical laboratory tests.
    • Physical, nasal and neurological examinations.
    • Vital sign measurements (systolic and diastolic blood pressure, pulse rate, respiration rate, and temperature) as recorded by the study center personnel.
    • Columbia-Suicide Severity Rating Scale (C-SSRS).
    • Requirement for unscheduled emergency room (ER) or emergency medical service (EMS) visits within 24 hours after study drug administration.
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject or subject's legally acceptable representative (LAR) has provided written informed consent, and subject has provided written
    assent where required by local law or Institutional Review Board (IRB) / Independent Ethics Committee (IEC) policy.
    2. Subject has a competent, adult (age ≥18 years) caregiver(s) who is able to recognize and observe the subject's seizure cluster episodes,
    who is willing to be trained in the study procedures, and has provided written informed consent; the caregiver(s) must be a relative, partner,
    friend, or LAR of the subject, or a person who provides daily care to the subject who has a significant personal relationship with the subject.
    3. Subject is 12 years of age or older at Visit 1.
    4. Subject has an established diagnosis of partial or generalized epilepsy.
    5. Subject has a documented history of seizure clusters that includes all the following:
    a. The subject's seizure cluster pattern is observable, stereotyped, and recognizably different from the subject's other non-cluster seizure
    activity (if any) in seizure type, duration, severity, or frequency, and of the same type that was approved by the central reviewer in study P261-
    401.
    b. A documented history of seizure clusters lasting a minimum of 10 minutes from the time the seizure cluster is recognized.
    c. As part of the subject's stereotyped seizure cluster pattern, a second seizure typically occurs within 6 hours from the time of recognition of the seizure cluster.
    d. The subject's stereotyped seizure cluster pattern is composed of multiple (≥2) partial or generalized seizures.
    e. The subject's stereotyped seizure cluster pattern was established > 3 months before Visit 1 of study P261-401.
    f. A frequency of ≥3 stereotyped seizure clusters during the year before Visit 1 of study P261-401.
    g. At least 1 stereotyped seizure cluster occurring at least once in the 4 months before Visit 1 of study P261-401.
    6. Subject has successfully completed study P261-401 and the subject and caregiver have demonstrated adequate compliance with P261-401 study procedures as determined by the investigator, OR, if Study P261-401 has been terminated, the subject completed the Test Dose Visit (Visit 2) of study P261-401 and the subject did not meet any Visit 2 exclusion criteria in study P261-401.
    7. Subject is not likely to conceive, as indicated by a ―yes‖answer to at least 1 of the following questions:
    a. Is the subject a male?
    b. Is the subject a postmenopausal female as determined in study P261-401?
    c. Is the subject a female who has written medical documentation of being permanently sterilized (e.g. hysterectomy, double oophorectomy,
    bilateral salpingectomy)?
    d. Has the subject agreed to use two effective methods of contraception during the entire study if she is sexually active or will become sexually active during the study (except where local law or regulation differs; approval by USL or designee is required in such cases)?
    Examples of two effective methods of contraception include the following:
    - A diaphragm and a condom with spermicide.
    - An intrauterine device (IUD) used in combination with a barrier method (e.g. condom, diaphragm, or cervical cap with spermicide).
    - Hormonal methods (e.g., high-dose birth control pills, Depo-Provera) or tubal ligation used in combination with a barrier method (e.g.,
    condom, diaphragm, or cervical cap with spermicide).
    Note that hormonal contraception alone is not considered adequate for this study and must be used in combination with another method. The
    type of birth control used must be approved by the investigator or designee.
    E.4Principal exclusion criteria
    1. Subject experienced a seizure cluster progressing to status epilepticus during or since his/her participation in Study P261-401.
    2. Subject has a positive pregnancy test at any visit or is pregnant, considering becoming pregnant, or is breastfeeding (female subjects
    only).
    3. Subject who, in the opinion of the investigator, is experiencing an ongoing, uncontrolled, clinically significant adverse event(s) from P261-
    401 at Visit 1 or did experience a clinically significant adverse event in study P261-401 that might prevent the subject from safely participating
    in the study.
    4. Subject has consumed any clinically significant CYP450 3A inhibitor/inducer, opioid, or other respiratory depressant, not including
    antiepileptic drugs (AEDs), within the required washout period before Visit 1
    5. Subjects using chronic benzodiazepine(s); chronic use is defined as use for 4 or more days in a 7-day period on average.
    6. Subject has a neurological disorder that is likely to progress in the next year.
    7. Subject has a history of acute narrow-angle glaucoma.
    8. Subject has a medical condition including uncontrolled cardiac, pulmonary, renal, hepatic, or gastrointestinal disease that could interfere with the study, subject safety/safety monitoring, or is not stable despite current therapy.
    9. Subject has severe chronic cardio-respiratory disease with baseline room air oxygen saturations < 90%, New York Heart Association class
    III or IV functional status, or the need for ambulatory oxygen.
    10. Subject has had psychogenic, non-epileptic seizure(s) during or since the P261-401 study.
    11. Subject has suicidality, defined as any of the following: a) active suicidal plan/intent or active suicidal thoughts during or since the P261-
    401 study as defined by a Columbia-Suicide Severity Rating Scale (CSSRS) suicidal ideation score ≥3, b) any suicide attempt during or since
    the P261-401 study as determined by the C-SSRS or medical history, or c) other clinically significant suicidality as determined by the investigator.
    12. Subject, in the investigator's opinion, has met the criteria for a major depressive episode during or since the P261-401 study (criteria defined
    by the current edition of the Diagnostic and Statistical Manual of Mental Disorders).
    13. Subject has or has had psychosis during or since the P261-401 study, excluding postictal psychosis
    14. Subject has a history of drug or alcohol abuse during or since study P261-401.
    E.5 End points
    E.5.1Primary end point(s)
    The following safety endpoints will be summarized using the Safety Population:
    • Treatment Emergent Adverse Events (TEAEs) will be presented by treatment received, severity, relationship to study drug and age group (< 18 vs. ≥18 years).
    • Clinical laboratory results will be presented by visit.
    • Vital sign measurements (systolic and diastolic blood pressure, pulse rate, respiration rate, and temperature) performed by study center staff will be summarized at each visit.
    • Caregiver-recorded respiration rate will be presented using descriptive statistics at each time point and for each treatment. The number of subjects who have < 8 breaths per minute and > 24 breaths per minute after study drug administration will be presented by time point and for each treatment.
    • Number of subjects requiring an unscheduled ER or EMS visit within 24 hours after study drug administration will be presented for each treatment.
    • Suicidal behavior and ideation using the C-SSRS will be summarized at each visit.
    • Physical, nasal and neurological examination results will be presented by visit.
    The following efficacy endpoints will be summarized using the Efficacy Evaluable Population:
    • Short and long term efficacy of USL261 as the outpatient treatment of seizure clusters based on Treatment Success based on appropriate longitudinal model
    • Kaplan-Meier analysis of time to return to baseline functionality
    E.5.1.1Timepoint(s) of evaluation of this end point
    • Treatment Emergent Adverse Events: Throughout the study
    • Clinical laboratory results and vital sign measurements: at each visit
    • Caregiver-recorded respiration rate: at 10, 15 and 30 minutes and 1, 2, and 4 hours after USL261 administration
    • Number of subjects requiring an unscheduled ER or EMS: within 24 hours after study drug administration
    • Suicidal behavior and ideation using the C-SSRS and physical, nasal and neurological examination results: At each visit
    • The proportion of subjects who achieve Kaplan-Meier analysis of time to return to baseline functionality: after study drug administration
    E.5.2Secondary end point(s)
    Not applicable
    E.5.2.1Timepoint(s) of evaluation of this end point
    Not applicable
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Open-Label Safety Study of USL 261
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    European Union
    Israel
    New Zealand
    Ukraine
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last Visit Last Subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 50
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 50
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 283
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 17
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Adolescent patients aged 14 to 17 years.
    Subjects with Legal Representative/cognitively impaired subjects
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 175
    F.4.2.2In the whole clinical trial 350
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    No difference to the expected normal treatment of that condition
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-07-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-07-31
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 01:22:55 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA