protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT04823611 | E | 7 References | E 7 References
Aithal et al, 2011 Aithal et al 2011, Clinical Pharmacology and Therapeutics 89(6):806-815.
FDA Guidance for Industry, July 2009 FDA Guidance for Industry (issued July 2009) 'Drug-induced liver injury: Premarketing clinical evaluation'. Available from; https://www.fda.gov/regulatory-information/search-... | [
"Aithal et al, 2011",
"FDA Guidance for Industry, July 2009",
"Appendix F Actions in Case of Development of Thrombocytopenia or Uninterpretable Platelet Counts After Administration of ASOs"
] |
NCT04823611 | F | 1 Actions in Case of Uninterpretable Platelet Count Results | F 1 Actions in Case of Uninterpretable Platelet Count Results Participants with uninterpretable platelet laboratory results due to clumping, haemolysis or quantity not sufficient must be reassessed within 2 days. Dosing is not allowed to proceed until the Investigator has determined that the results are within acceptab... | [
"Thrombocyte Monitoring Frequency",
"Additional Laboratory Assessments (Platelet Count < 75,000/μL)"
] |
NCT04823611 | F | 2 Referral to Expert Haematologist Care | F 2 Referral to Expert Haematologist Care Participants that develop thrombocytopenia with platelet counts ≤ 50,000/µL should be referred to a haematologist for diagnostic and therapeutic management. This may include the additional laboratory tests described in the table above. Additional bone marrow aspiration and biop... | [
"Supportive Treatment with Corticosteroids"
] |
NCT04823611 | F | 3 Reference | F 3 Reference
Provan et al, 2010 Provan D et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168-186.
Appendix G Guidance for Definition of Anaphylactic/Hypersensitivity Reactions and Checklist for the Investigator The National Institute of... | [
"Provan et al, 2010",
"Appendix G Guidance for Definition of Anaphylactic/Hypersensitivity Reactions and Checklist for the Investigator",
"Hypersensitivity Reactions – Checklist for the Investigator",
"Additional Samples to be Collected in Case of an Anaphylactic-like Reaction"
] |
NCT04823611 | G | 1 Reference | G 1 Reference
Sampson et al, 2006 Sampson HA et al. Second symposium on the definition and management of anaphylaxis: Summary report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391-397.
Appendix H Statin Therapy - atorv... | [
"Sampson et al, 2006",
"Appendix H Statin Therapy",
"Appendix I Abbreviations",
"11 REFERENCES",
"Burdick AD et al 2014",
"Burel S et al 2013",
"Cohen J et al 2005",
"Cohen J et al 2006",
"Collins R et al 2016",
"Crooke ST et al 2016",
"Crooke ST et al 2017",
"Hagedorn PH et al 2013",
"Henry... |
NCT04836559 | 1 | PROTOCOL SUMMARY | 1. PROTOCOL SUMMARY | [] |
NCT04836559 | 1.1 | Synopsisa | 1.1. Synopsisa A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-40411813 as Adjunctive Therapy in Subjects with Focal Onset Seizures with Suboptimal Response to Levetiracetam or Brivaracetam
Background: JNJ-40411813 is a positiv... | [
"Background:",
"OBJECTIVES AND HYPOTHESIS",
"Primary Objective",
"Secondary Objectives",
"Exploratory Objectives",
"Hypothesis",
"OVERVIEW OF STUDY DESIGN",
"PARTICIPANT POPULATION",
"DOSAGE AND ADMINISTRATION",
"EFFICACY EVALUATIONS",
"PHARMACOKINETIC EVALUATIONS",
"SAFETY EVALUATIONS",
"ST... |
NCT04836559 | 1 | 2, Schedule of Activities (SoA)? | 1.2, Schedule of Activities (SoA)? | Periods | Screening | Baseline | | | | Double-blind treatment | | Follow-up | |---------------------------------------------------------------------------------------------|-----------|------------|----|--|-------------|------------------------|------------------------------|-------... | [
"Footnotes:"
] |
NCT04836559 | 2 | INTRODUCTION | 2. INTRODUCTION JNJ-40411813 is a positive allosteric modulator (PAM) of the metabotropic glutamate receptor-2 (mGlu2), which is abundantly expressed in the forebrain and cerebellum. The mGlu2 receptor functions as a presynaptic auto-receptor that, upon activation, decreases the release of the excitatory neurotransmitt... | [] |
NCT04836559 | 2.1 | Study Rationale | 2.1. Study Rationale Based on nonclinical data JNJ-40411813 is expected to show synergistic activity with levetiracetam or brivaracetam, which is thought to bind to and regulate Synaptic Vesicle glycoprotein 2a (SV2a), a vesicular protein in the presynaptic terminal involved in glutamate release (Metcalf 2017, 2018). I... | [] |
NCT04836559 | 2.2 | Background | 2.2. Background | [] |
NCT04836559 | 2.2.1 | Nonclinical Studiesa | 2.2.1. Nonclinical Studiesa
Nonclinical pharmacology The in vitro potency (as effective concentration [EC50]) is 100 nM on human mGlu2 based on several cellular read-outs (Lavreysen 2015). aThis section has been amended by Amendment INT-2 JNJ-40411813 antagonized the serotonin type 2A (5-HT2A) receptor with moderate p... | [
"Nonclinical pharmacology",
"Toxicology",
"Pharmacokinetics and Metabolism in Animals"
] |
NCT04836559 | 2.2.2 | Clinical Studies | 2.2.2. Clinical Studies did not show any potential as To date, 9 Phase 1 clinical studies have been completed including a total of 345 healthy subjects, a Phase 2 study of 100 subjects with schizophrenia, and a Phase 2 study of 121 subjects with Major Depressive Disorder (MDD) with anxiety symptoms.
Pharmacokinetics, ... | [
"Pharmacokinetics, Product Metabolism, and Pharmacodynamics",
"Safety and Tolerability"
] |
NCT04836559 | 2.2.3 | Brivaracetam | 2.2.3. Brivaracetam Brivaracetam is an antiepileptic drug indicated as adjunctive therapy in the treatment of partialonset seizures in patients 16 years of age and older with epilepsy. Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A), a transmembrane glycoprotein found at presy... | [] |
NCT04836559 | 2.2.4 | Levetiracetam | 2.2.4. Levetiracetam Levetiracetam is an antiepileptic drug. Its mechanism of action is modulation of synaptic neurotransmitter release through binding to the synaptic vesicle glycoprotein SV2a in the brain. Levetiracetam is a generic drug, where several different formulations are available. The daily starting dose in ... | [] |
NCT04836559 | 2.3 | Benefit/Risk Assessment | 2.3. Benefit/Risk Assessment | [] |
NCT04836559 | 2.3.1 | Risks for Study Participation | 2.3.1. Risks for Study Participation | Potential Risks of ClinicalSignificance | Summary of Data/Rationale for Risk | Mitigation Strategy | |-------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04836559 | 2.3.2 | Benefits for Study Participationa | 2.3.2. Benefits for Study Participationa Treatment resistant epilepsy has a severe impact on quality of life and risk of mortality. JNJ-40411813 in combination with levetiracetam or brivaracetam shows promise in a nonclinical model of epilepsy and – if proven efficacious in man too –may result in a significant positive... | [] |
NCT04836559 | 2.3.3 | Benefit-Risk Assessment for Study Participation | 2.3.3. Benefit-Risk Assessment for Study Participation The risk/benefit of JNJ-40411813 is favorable and the currently available safety and efficacy data support the proposed clinical trial 40411813EPY2001 to investigate efficacy and safety of JNJ-40411813 in participants with focal onset epilepsy. More detailed inform... | [] |
NCT04836559 | 3 | OBJECTIVESAND ENDPOINTSa | 3. OBJECTIVESAND ENDPOINTSa | Objectives | Endpoints | |------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [
"CONFIDENTIAL — FOIA Exemptions Apply in U.S. 28",
"Hypothesis"
] |
NCT04836559 | 4 | STUDY DESIGN | 4. STUDY DESIGN | [] |
NCT04836559 | 4.1 | Overall Designa | 4.1. Overall Designa This study as per Amendment INT-2 will consist of a double-blind treatment period and an openlabel extension (OLE) period. Details about the OLE period are described in Section 10. This is a double-blind, randomized, parallel, placebo-controlled study with the option for an OLE period. The study wi... | [
"Follow-up examination or early withdrawal",
"Design aspects and placebo control",
"Stratification JNJ-40411813 is metabolized mainly by CYP3A4. CCI",
"Optional dosage reduction",
"Time to baseline monthly seizure count as an endpoint",
"Combination with levetiracetam and brivaracetam.",
"Study populati... |
NCT04836559 | 4.2.1 | Study-Specific Ethical Design Considerations | 4.2.1. Study-Specific Ethical Design Considerations Potential participants will be fully informed of the risks and requirements of the study and, during the study, participants will be given any new information that may affect their decision to continue participation. They will be told that their consent to participate... | [] |
NCT04836559 | 4.4 | End of Study Definitiona | 4.4. End of Study Definitiona
End of Study Definition for the double-blind period. The end of study for the double-blind period is considered as the last visit for Visit 7 for the last participant in the study. The final data for the double-blind period from the study site will be sent to the sponsor (or designee) aft... | [
"End of Study Definition for the double-blind period."
] |
NCT04836559 | 5 | STUDY POPULATION | 5. STUDY POPULATION For the first cohort, approximately 80 eligible participants will be initially included to ensure that approximately 60 participants are randomly assigned in a 2:1 ratio to receive either JNJ-40411813 or placebo. For each following cohort, approximately 60 eligible participants will be initially enr... | [] |
NCT04836559 | 5.1 | Inclusion Criteriab | 5.1. Inclusion Criteriab Each potential participant must satisfy all the following criteria to be enrolled in the study.
Epilepsy related inclusion criteria - 1. Participants must be men or women, 18 to 69 years of age, inclusive. - Note: Participants should be at least 18 years of age or older as per the legal age of... | [
"Epilepsy related inclusion criteria",
"Other inclusion criteria"
] |
NCT04836559 | 5.2 | Exclusion Criteriaa | 5.2. Exclusion Criteriaa
Epilepsy related exclusion criteria - 1. Have a generalized epileptic syndrome. - 2. Diagnosis of Lennox-Gastaut Syndrome. - 3. Currently experiencing seizures that cannot be counted accurately, for example, because of the following reasons: - Extreme frequency or clustering. - Lack of clear o... | [
"Epilepsy related exclusion criteria",
"Other exclusion criteria"
] |
NCT04836559 | 5.3 | Lifestyle Considerations | 5.3. Lifestyle Considerations Potential participants must be willing and able to adhere to the following lifestyle restrictions during the course of the study to be eligible for participation: 1. Refer to Section 6.5, Concomitant Therapy for details regarding prohibited and restricted therapy during the study. 2. Agree... | [] |
NCT04836559 | 5.3.1 | Meals and Dietary Restrictions | 5.3.1. Meals and Dietary Restrictions - 1. Participants may not consume any food or beverages containing, grapefruit juice, Seville oranges (including any orange marmalade), or quinine (e.g., tonic water) from 48 hours (72 hours in the case of grapefruit juice and Seville oranges) before the first dose of study interve... | [] |
NCT04836559 | 5.3.2 | Caffeine, Alcohol, and Tobacco | 5.3.2. Caffeine, Alcohol, and Tobacco - 1. Participants should abstain from using excessive alcohol or any illegal drugs within 3 days prior to Day 1 and at any time during the study. Current low to moderate use of alcohol as approved by the investigator may be continued unchanged. - 2. The participant will be advised ... | [] |
NCT04836559 | 5.3.3 | Activity | 5.3.3. Activity - 1. Should avoid driving or operating complex machinery until the participant knows whether the drug adversely affects reaction time or impairs judgment. - 2. Participants must avoid donating blood for at least 90 days after completion (i.e., final followup visit) of the study. | [] |
NCT04836559 | 5.4 | Screen Failuresa | 5.4. Screen Failuresa
Participant Identification, Enrollment, and Screening Logs The investigator agrees to complete a participant identification and enrollment log to permit easy identification of each participant during and after the study. This document will be reviewed by the sponsor study-site contact for complet... | [
"Participant Identification, Enrollment, and Screening Logs"
] |
NCT04836559 | 6 | STUDY INTERVENTIONS | 6. STUDY INTERVENTIONS For description of the study intervention in the OLE period, see Section 10.6. | [] |
NCT04836559 | 6.1 | Study interventions Administereda | 6.1. Study interventions Administereda JNJ-40411813 will be supplied for this study as 25-mg and 50-mg tablets. Placebo will be supplied as matching tablets. The tablets will be taken from Day 1 to Day 85 (or day of Visit 7 when before Day 85). All study intervention, apart from the study intervention taken in the clin... | [] |
NCT04836559 | 6.2 | Preparation, Handling, and Storage | 6.2. Preparation, Handling, and Storage All study intervention will be manufactured and provided under the responsibility of the sponsor. All study intervention will be provided in child-resistant high-density polyethylene bottles. All study intervention will be stored in a secure area with restricted access. Tablets m... | [] |
NCT04836559 | 6.3 | Measures to Minimize Bias: Randomization and Blindinga | 6.3. Measures to Minimize Bias: Randomization and Blindinga
Procedures for Randomization Central randomization will be implemented in this study. Participants will be randomly assigned to one of two treatment groups based on computer-generated randomization schedules prepared before the study by, or under the supervis... | [
"Procedures for Randomization",
"Blinding"
] |
NCT04836559 | 6.4 | Study Intervention Compliancea | 6.4. Study Intervention Compliancea Study intervention will be taken by the participant at home or during a study visit in the clinic. The first dose will be taken by the participant at Visit 2 (Day 1) of the study in the clinic. The participant will be instructed to take their study intervention to the clinic at each ... | [] |
NCT04836559 | 6.5 | Concomitant Therapyb | 6.5. Concomitant Therapyb All prestudy therapies administered up to 30 days before screening must be recorded at screening (and confirmed by treating physician). During the 8-week prospective pretreatment baseline period and during the 12-week double-blind treatment period, participants will continue to take their pres... | [] |
NCT04836559 | 6.6 | Recording of drug intake; overview | 6.6. Recording of drug intake; overview The participant will receive an e-diary to record the intake of the study intervention. In the e-diary, only confirmation of intake of study medication and rescue medication are recorded. The time of intake will not be recorded in the e-diary. Intake of rescue medication should a... | [] |
NCT04836559 | 6.7 | Intervention After the End of the Studya | 6.7. Intervention After the End of the Studya Investigators may re-contact the participant to obtain follow-up information regarding the participants' safety if there are any safety concerns at the last study visit. Participants should continue taking the AEDs they were using during the study until such time as changes... | [] |
NCT04836559 | 7 | DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL | 7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL If a participant discontinues study intervention or withdraws from the study before the end of the double-blind period, the early withdrawal assessments (Visit 7) should be obtained. | [] |
NCT04836559 | 7.1 | Safety Data Review | 7.1. Safety Data Review Continuous or periodic blinded safety reviews will be done by the SRP. An unblinded review of the data (on the individual participant level) will be conducted if there are safety concerns from this blinded review as a result of severe, serious or unexpected AEs that are at least possibly related... | [] |
NCT04836559 | 7.2 | Completion | 7.2. Completion A participant will be considered to have completed the double-blind period of the study if he or she has completed the double-blind period up to Week 12 or has elected to exit after reaching the baseline monthly seizure count by Day 28 or exceeding the monthly baseline seizure count during a moving 28-d... | [] |
NCT04836559 | 7.3 | Participant Discontinuation/Withdrawal from the Studya | 7.3. Participant Discontinuation/Withdrawal from the Studya A participant will be withdrawn from the study for any of the following reasons. The participant must discontinue the study intervention and, whenever possible, the early withdrawal visit must be completed. Lost to follow-up aThis section has been amended by A... | [] |
NCT04836559 | 7.4 | Protocol Stopping Criteria | 7.4. Protocol Stopping Criteria Blinded medical monitoring by the sponsor will occur on a continuous basis including AEs, laboratory and ECG data. When there is any concern about the safety of the participants as a result of severe or serious AEs that are at least possibly related to JNJ-40411813 or if the frequency of... | [] |
NCT04836559 | 7.5 | Withdrawal from the Use of Research Samples | 7.5. Withdrawal from the Use of Research Samples The participant may withdraw consent for use of samples for research (refer to Long-Term Retention of Samples for Additional Future Research in Section 11.3). In such a case, samples will be destroyed after they are no longer needed for the clinical study. Details of the... | [] |
NCT04836559 | 7.6 | Lost to Follow-up | 7.6. Lost to Follow-up If a participant is lost to follow-up, every reasonable effort must be made by the study site personnel to contact the participant and determine the reason for discontinuation/withdrawal. The measures taken to follow-up must be documented. Refer to Section 7.3, Participant Discontinuation/Withdra... | [] |
NCT04836559 | 8 | STUDY ASSESSMENTS AND PROCEDURES | 8. STUDY ASSESSMENTS AND PROCEDURES For study assessments and procedures in the OLE period, see Section 10.8 | [] |
NCT04836559 | 8.1 | Overviewa | 8.1. Overviewa The SoA summarizes the frequency and timing ofall assessments applicable to this study. Repeat or unscheduled blood samples may be taken for safety reasons, additional PK samples or for technical issues with the samples. Additional serum (by local laboratory) or urine pregnancy tests may be performed, as... | [
"Sample Collection and Handling",
"Study-Specific Materials"
] |
NCT04836559 | 8.2 | Study procedures | 8.2. Study procedures | [] |
NCT04836559 | 8.2.1 | Screeninga | 8.2.1. Screeninga Participants will report to the clinical study center for the eligibility screening assessment just prior to the start of the 8-week baseline period. Participants will be asked to bring their current AEDs with them. Before any study specific procedures are conducted and following an explanation of the... | [] |
NCT04836559 | 8.2.2 | Baseline perioda | 8.2.2. Baseline perioda After screening, if they meet the in- and exclusion criteria for which data are available, participants can start the 8-week prospective pretreatment baseline period pending the results of the central laboratory and the adjudication process. However, when the results of these assessments indicat... | [] |
NCT04836559 | 8.2.3 | Treatment Perioda | 8.2.3. Treatment Perioda Participants who complete the baseline period will be asked to come to the study center for Visit 2. Visit 2 should be planned in the morning hours, before noon (12.00 pm). Participants must report seizures in the e-diary from Day 1 through the following double-blind treatment period. When poss... | [] |
NCT04836559 | 8.2.4 | Follow-up/Early Withdrawal Visit | 8.2.4. Follow-up/Early Withdrawal Visit For participants who will participate in the OLE period, no follow-up visit will be performed. For details see Section 10.4. All participants who discontinue the study before Week 12 are encouraged to complete the early withdrawal visit (Visit 7, Week 12/Early Withdrawal). The pr... | [] |
NCT04836559 | 8.3 | Efficacy Assessments | 8.3. Efficacy Assessments | [] |
NCT04836559 | 8.3.1 | Seizure counta | 8.3.1. Seizure counta The primary efficacy evaluation will be the time to baseline monthly seizure count. To assess this endpoint, the number and type of seizures during the baseline period and during the double-blind treatment period needs to be documented carefully. The participant and/or caregiver will be provided a... | [] |
NCT04836559 | 8.3.2 | Secondary Evaluationsa | 8.3.2. Secondary Evaluationsa | 8.3.2.1.CCI | |---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04836559 | 8.4 | Safety Assessments | 8.4. Safety Assessments | [] |
NCT04836559 | 8.4.1 | Physical Examination | 8.4.1. Physical Examination before being weighed. (Note: if disrobing for weighing is logistically impossible, the participant should be dressed as lightly as possible, with consistency from visit to visit). | [] |
NCT04836559 | 8.4.2 | Vital Signs | 8.4.2. Vital Signs Blood pressure measurements will be assessed in supine positions with a completely automated device. Manual techniques will be used only if an automated device is not available. Supine blood pressure measurements should be preceded by at least 5 minutes of rest in a quiet setting without distractions... | [] |
NCT04836559 | 8.4.3 | Electrocardiogram (ECG)a | 8.4.3. Electrocardiogram (ECG)a At screening, a triplicate ECG recording is required, i.e., 3 individual ECG tracings should be obtained as closely as possible in succession, but no more than 2 minutes apart. The full set of triplicates should be completed in less than 4 minutes. At the other visits indicated in the So... | [] |
NCT04836559 | 8.4.4 | Clinical Safety Laboratory Assessments | 8.4.4. Clinical Safety Laboratory Assessments Blood samples for serum chemistry and hematology and a random urine sample for urinalysis will be collected as noted in Section 11.2, Clinical Laboratory Tests. A central laboratory will be used for testing. The investigator must review the laboratory results, document this... | [] |
NCT04836559 | 8.4.5 | Suicidal Risk Monitoring | 8.4.5. Suicidal Risk Monitoring JNJ-40411813 is considered to be a CNS-active compound. The sponsor considers it important to monitor for such events before and during this clinical study.
Columbia Suicide Severity Rating Scale (C-SSRS) An interview to assess the risk of suicidal ideation and behavior will be conducte... | [
"Columbia Suicide Severity Rating Scale (C-SSRS)"
] |
NCT04836559 | 8.5 | Pharmacokineticsa | 8.5. Pharmacokineticsa  aThis section has been amended by Amendment INT-1 and INT-3 | Studyvisit | StudyDay | JNJ-40411813 andmetabolitesRelative to in-clinic dose | Brivaracetam orLevetiracetamRelative to in-clinic dose | CCI | |----------------|--------------|-----------------------------------... | [] |
NCT04836559 | 8.6 | Genetics | 8.6. Genetics  \If the subject is taking levetiracetam XR once daily in the evening, then one PK sample for levetiracetam will be collected on Visits 2 and 4 (at the same time as the postdose sample for JNJ-40411813) and Visit 6 (at the same time as the predose sample for JNJ-40411813)  Additional instructions for collection ofbiomarker samples: CCI - Blood biomarkers will be collected under fasting conditions –at least 4 hours, water permitted with th... | [
"Participant data"
] |
NCT04836559 | 8.8 | Adverse Events and Serious Adverse Events | 8.8. Adverse Events and Serious Adverse Events Timely, accurate, and complete reporting and analysis of safety information from clinical studies are crucial for the protection of participants, investigators, and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established Standard Operati... | [
"Adverse Events of Interest"
] |
NCT04836559 | 8.8.1 | Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event Information | 8.8.1. Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event Information
All Adverse Events All AEs and special reporting situations, whether serious or non-serious, will be reported from the time a signed and dated ICF is obtained until completion of the participant's last study visit, whic... | [
"All Adverse Events",
"Serious Adverse Events"
] |
NCT04836559 | 8.8.2 | Follow-up of Adverse Events and Serious Adverse Events | 8.8.2. Follow-up of Adverse Events and Serious Adverse Events AEs, including pregnancy, will be followed by the investigator as specified in Section 11.4, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting. | [] |
NCT04836559 | 8.8.3 | Regulatory Reporting Requirements for Serious Adverse Events and Anticipated Events | 8.8.3. Regulatory Reporting Requirements for Serious Adverse Events and Anticipated Events The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. The sponsor will also report to the investigator (and the head of the investigational institute where required) all suspected unex... | [] |
NCT04836559 | 8.8.4 | Pregnancy | 8.8.4. Pregnancy All initial reports of pregnancy in female participants or partners of male participants must be reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the event using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (e.g., spontaneous abortion... | [] |
NCT04836559 | 8.9 | Treatment of Overdose | 8.9. Treatment of Overdose For this study, any single dose of JNJ-40411813 greater than a 24-hour time period will be considered an overdose. The sponsor does not recommend specific intervention for an overdose. CCI In the event of an overdose, the investigator or treating physician should: - Contact the Medical Monito... | [] |
NCT04836559 | 9 | STATISTICAL CONSIDERATIONS | 9. STATISTICAL CONSIDERATIONS The double-blind study period will be analyzed separately from the OLE period after completion of the double-blind period for each cohort. | [] |
NCT04836559 | 9.1 | Sample Size Determination | 9.1. Sample Size Determination The calculation of the maximum sample size planned for this study was simulation-based and was estimated using a Cox's proportional hazard regression model comparing the time to baseline seizure count between JNJ-40411813 and placebo. A longitudinal model for individual daily seizure coun... | [] |
NCT04836559 | 9.2 | Efficacy analyses | 9.2. Efficacy analyses | [] |
NCT04836559 | 9.2.1 | Primarya | 9.2.1. Primarya The intent-to-treat population will be the primary efficacy population, which includes all participants who are randomly assigned to receive study drug and who have baseline and postbaseline seizure data. Data from participants on placebo in cohorts 2 and 3 will be combined with those from Cohort 1 if t... | [] |
NCT04836559 | 9.2.2 | Secondary and exploratorya | 9.2.2. Secondary and exploratorya Secondary efficacy endpoints will be subject to an exploratory analysis including descriptive statistics by treatment arm and graphical exploration. Details of the analysis for each secondary endpoint and exploratory endpoints will be provided in the SAP. aThis section has been amended... | [
"Seizure Freedom",
"Secondary generalized seizures",
"Responder rate"
] |
NCT04836559 | 9.3 | PKand PK/PD analysesa | 9.3. PKand PK/PD analysesa Data for all participants who receive a dose of JNJ-40411813 and have at least one measurement of plasma concentration, will be included in the PK analysis. Plasma concentrations of JNJ-40411813 and metabolites including levetiracetam/ brivaracetam and will CCI CCI be listed for all participa... | [] |
NCT04836559 | 9.4 | Safety Analysesa | 9.4. Safety Analysesa Statistical analysis of the safety data will be done by the sponsor or under the authority of the sponsor. Specific details will be provided in the Statistical Analysis Plan. All safety analyses will be performed based on the safety analysis set, which will include all included participants who re... | [
"Adverse Events",
"Clinical Laboratory Tests",
"ECG",
"Vital Signs",
"Physical and Neurological Examinations",
"Other Safety Measures",
"C-SSRS"
] |
NCT04836559 | 9.5 | Data Reviewafter each cohorta | 9.5. Data Reviewafter each cohorta After at least 55 patients in Cohort 1 and after at least 45 patients in Cohort 2 have completed at least 4 weeks of treatment, an interim unblinded review of all cumulative safety, PK, and efficacy data of JNJ-40411813 available to that date will be performed to decide on whether the... | [] |
NCT04836559 | 10 | ADDENDUM FOR OPEN-LABEL EXTENSION (OLE) PERIODa | 10. ADDENDUM FOR OPEN-LABEL EXTENSION (OLE) PERIODa | [] |
NCT04836559 | 10.1 | Rationale | 10.1. Rationale This is an OLE period to investigate the long-term safety and efficacy of JNJ-40411813 in subjects who completed their participation in the double-blind study period. This study period will allow study participants to continue treatment and evaluate long-term safety and efficacy of JNJ-40411813 in epile... | [] |
NCT04836559 | 10.2 | Benefit/Risk Assessment of the OLE period | 10.2. Benefit/Risk Assessment of the OLE period | [] |
NCT04836559 | 10.2.1 | Risks for Participation | 10.2.1. Risks for Participation | Potential Risks of ClinicalSignificance | Summary of Data/Rationale for Risk | Mitigation Strategy | |-----------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------... | [] |
NCT04836559 | 10.2.2 | Benefits for Participation | 10.2.2. Benefits for Participation Treatment-resistant epilepsy has a severe impact on quality of life and risk of mortality. JNJ-40411813 in combination with levetiracetam shows promise in a nonclinical model of epilepsy and –if proven efficacious in man too –may result in a significant positive impact on this patient... | [] |
NCT04836559 | 10.2.3 | Benefit-Risk Assessment | 10.2.3. Benefit-Risk Assessment The risk/benefit of JNJ-40411813 is favorable and the currently available safety and efficacy data support the proposed open-label study period to investigate the long-term efficacy and safety of JNJ-40411813 in participants with focal onset epilepsy. More detailed information about the ... | [] |
NCT04836559 | 10.3 | Objectives and endpoints of OLE period | 10.3. Objectives and endpoints of OLE period | Objectives | Endpoints | |-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------... | [
"Hypothesis"
] |
NCT04836559 | 10.4 | Design of the OLE period | 10.4. Design of the OLE period | [] |
NCT04836559 | 10.4.1 | Overall Design | 10.4.1. Overall Design
Overview of the open-label period: For each participant, the open-label period will start immediately after the last study drug intake by the participant in the double-blind period. Participants participating in this open-label period will not have the follow-up visit (Visit 8) as mentioned in t... | [
"Overview of the open-label period:",
"Withdrawal",
"Combination with levetiracetam or brivaracetam",
"Study population",
"Duration of the study",
"Pharmacokinetics"
] |
NCT04836559 | 10.4.3 | Study-Specific Ethical Design Considerations | 10.4.3. Study-Specific Ethical Design Considerations For the open-label period: The primary ethical concern is the long-term use of JNJ-40411813 as an experimental treatment in epilepsy. The compound has been used in several clinical studies in healthy subjects and patient populations (see IB) and was generally well to... | [] |
NCT04836559 | 10.4.4 | Justification for dose | 10.4.4. Justification for dose No fixed dose schedule will be presented for this study. All participants will start with intake of JNJ-40411813 at the same dose they used in the double-blind study period. See also Section 4.1. | [] |
NCT04836559 | 10.4.5 | End of Study Definition | 10.4.5. End of Study Definition
End of Study Definition for the OLE period. The end of study for the OLE period is considered as the last visit for Visit OLE 11 or OLE12 for the last participant in the study. The final data for the OLE period from the study site will be sent to the sponsor (or designee) after completi... | [
"End of Study Definition for the OLE period."
] |
NCT04836559 | 10.5 | Study population for the OLE period | 10.5. Study population for the OLE period No fixed number of participants has been defined for this OLE period. The inclusion and exclusion criteria for enrolling participants in this open-label study period are described in the following sections. If there is a question about the inclusion or exclusion criteria below,... | [] |
NCT04836559 | 10.5.1 | Inclusion Criteria | 10.5.1. Inclusion Criteria Each potential participant must satisfy all the following criteria to be enrolled in the open-label study period. - 101. The participant must have participated in the double-blind treatment period. This also includes participants who stopped during the double-blind treatment period because th... | [] |
NCT04836559 | 10.5.2 | Exclusion Criteria | 10.5.2. Exclusion Criteria - 106. Participant meets any of the withdrawal criteria during the double-blind period or is experiencing an ongoing severe or serious adverse event considered related to study medication by the investigator. - 107. Participant is receiving any investigational drug or using any experimental d... | [] |
NCT04836559 | 10.5.3 | Lifestyle Considerations | 10.5.3. Lifestyle Considerations Potential participants must be willing and able to adhere to the following lifestyle restrictions during the course of the study to be eligible for participation: - 109. Refer to the Section 6.5 on Concomitant Therapy for details regarding prohibited and restricted therapy during the st... | [] |
NCT04836559 | 10.6 | Study interventions | 10.6. Study interventions | [] |
NCT04836559 | 10.6.1 | Study interventions Administered | 10.6.1. Study interventions Administered JNJ-40411813 will be supplied for this OLE period as 25-mg and 50-mg tablets. . Only on the days of study visits, participants will not take the study drug at home, but will take the study drug with them to the clinic and take the study medication in the clinic after the collect... | [] |
NCT04836559 | 10.6.2 | Preparation, Handling, and Storage | 10.6.2. Preparation, Handling, and Storage See Section 6.2. | [] |
NCT04836559 | 10.6.3 | Measures to Minimize Bias: Randomization and Blinding | 10.6.3. Measures to Minimize Bias: Randomization and Blinding No randomization procedure will be applied in the open-label period. Participants completing the double-blind period and starting the open-label period will not be unblinded. Participants who had been receiving placebo will start with the JNJ-40411813 dose t... | [] |
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