Study of Safety and Efficacy of MGCND00EP1 as an Add on Treatment in Children and Adolescents With Resistant Epilepsies
NCT ID: NCT04406948
Last Updated: 2024-06-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE2
INTERVENTIONAL
2024-05-30
2024-05-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Objective:To evaluate the safety and efficacy of: MGCND00EP1 from MGC PHARMACEUTICALS d.o.o.
Study Design: Randomized, double blind, placebo controlled parallel grouped study Sample Size: 103 subjects Study Population: Children from 1 year to 18 years of age Comparator Product :Placebo solution, oral IMP Product : MGCND00EP1 (each ml of solution containing 100 mg of cannabidiol and 5 mg of (-)-trans-Δ9- tetrahydrocannabinol as active substance) from MGC PHARMACEUTICALS D.O.O.
According to dosing scheme up to 25 mg/kg BW per day or maximum daily dose 800 mg (whichever smaller) for 6 weeks titration and 6 weeks of treatment, oral administration
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures
NCT02477839
Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures
NCT03336242
Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
NCT00692003
Efficacy and Safety of Adjunctive Zonisamide in Myoclonic Seizures Associated With Idiopathic Generalised Epilepsy
NCT00693017
Efficacy and Safety of GWP42003-P Oral Solution in Children With Epilepsy With Myoclonic-atonic Seizures
NCT05288283
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Day one - Screening and Enrollment Visit :
Total 103 patients: Obtain informed consent from legal guardian. Screen potential subjects by inclusion and exclusion criteria. Visit 1: obtain medical and medication history, vital signs, physical and neurological exam, blood and urine tests, ECG, EEG, concomitant medications, questionnaires.
Weeks 1-4 - AED Stabilization Period :
Visit 2: vital signs, weight, physical and neurological exam, blood and urine tests, concomitant medications, questionnaires, monitor AEs, PK blood collection (subset of patients), randomize and dispense study drugs
Patients will be randomized and will either get placebo or MGCND00EP1 (3:1 active:placebo)
Weeks 5-10 - Dose titration period:
Dose escalations (2 mg/kg body weight/day increments), as required, up to 25 mg/kg/day or 800 mg/day, the lower of the two, until stable dose is reached.
Visit 3: vital signs, weight, physical and neurological exam, blood and urine tests, concomitant medications, questionnaires, collect and issue diaries, dispense study drug, monitor AEs
Weeks 11-16 - Maintenance Period :
Visit 4: vital signs,weight, physical and neurological exam, blood and urine tests, concomitant medications, questionnaires, PK sample collection (subset of patients), collect and issue diaries, dispense study drug, EEG, monitor AEs
Weeks 17-18 - Tapering-off and Follow-up Period:
Weekly phone call to determine taper dose at physician's discretion
Visit 5: vital signs,weight, physical and neurological exam, blood and urine tests, concomitant medications, questionnaires, monitor AEs, collect diaries and unused drug
Weeks 19-20 - Follow-up Period:
Weekly phone calls
Visits 6: vital signs,weight, physical and neurological exam, concomitant medications, monitor AEs, collect diaries .
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
* Add on treatment 42 days (6 weeks) - titration period - MGCND00EP1 or placebo in addition to AE medications.
* Add on treatment 42 days (6 weeks) Maintenance stable treatment period - MGCND00EP1 or placebo in addition to AE medications
* Add on treatment 14 days (2 weeks)- taper - down titration period - MGCND00EP1 or placebo in addition to AE medications
* Follow up 28 days - Standard/ previous AE treatment
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
MGCND00EP1
Participants who will assigned to receive add on MGCND00EP1 will receive carrier oil containing THC and CBD in ratio 20:1, (10% of cannabidiol and 0.5 % and (-)-trans-Δ9-tetrahydrocannabinol) .
Titration Dose: 1 to 2 mg/kg body weight/day. dose will be increased every week by 2 mg/kg body weight/day up to a maximum 25 mg/kg body weigh/day or maximum daily dose 800 mg (the smaller of those 2 values) (divided into two daily doses).
After titration, patients will be receiving a stable maintenance dose of IMP (up to 25 mg/kg BW per day or maximum daily dose 800 mg (whichever smaller)) for 6 weeks period.
During forth treatment period participants will commence a 2 weeks down-titration taper period, followed by 4 weeks observational follow up period of previous standard AE treatment without IMP.
MGCND00EP1
Patients will take cannabis oil during the study
ECG
A standard 12-lead ECG will be recorded using digital ECG recording equipment provided to the investigational site. The ECG has to be performed prior to laboratory samplings at time points indicated in the Schedule of Assessments.
The ECG recording will be reviewed by investigator and case of need consultation with cardiologist will be performed. The investigator has the final decision on the clinical significance of the ECG results.
EEG
An EEG is an electrophysiological monitoring method that records the electrical activity and measures voltage fluctuations resulting from ionic current within the neurons of the brain. In clinical contexts, EEG refers to the recording of the brain's spontaneous electrical activity over a period of time.
Blood and urine collection
safety blood tests - hematology\\blood count and biochemistry standard blood tests urinalysis - urine test analysis
PLACEBO
Participants who are assigned to receive add on PLACEBO will be administered the carrier oil (without the active ingredients).
Titration Dose: 1 to 2 mg/kg body weight/day. dose will be increased every week by 2 mg/kg body weight/day up to a maximum 25 mg/kg body weigh/day or maximum daily dose 800 mg (the smaller of those 2 values) (divided into two daily doses).
After titration, patients will be receiving a stable maintenance dose of IMP (up to 25 mg/kg BW per day or maximum daily dose 800 mg (whichever smaller)) for 6 weeks period.
During forth treatment period participants will commence a 2 weeks down-titration taper period, followed by 4 weeks observational follow up period of previous standard AE treatment without IMP.
Placebo
Patient will take carrier oil during the study
ECG
A standard 12-lead ECG will be recorded using digital ECG recording equipment provided to the investigational site. The ECG has to be performed prior to laboratory samplings at time points indicated in the Schedule of Assessments.
The ECG recording will be reviewed by investigator and case of need consultation with cardiologist will be performed. The investigator has the final decision on the clinical significance of the ECG results.
EEG
An EEG is an electrophysiological monitoring method that records the electrical activity and measures voltage fluctuations resulting from ionic current within the neurons of the brain. In clinical contexts, EEG refers to the recording of the brain's spontaneous electrical activity over a period of time.
Blood and urine collection
safety blood tests - hematology\\blood count and biochemistry standard blood tests urinalysis - urine test analysis
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
MGCND00EP1
Patients will take cannabis oil during the study
Placebo
Patient will take carrier oil during the study
ECG
A standard 12-lead ECG will be recorded using digital ECG recording equipment provided to the investigational site. The ECG has to be performed prior to laboratory samplings at time points indicated in the Schedule of Assessments.
The ECG recording will be reviewed by investigator and case of need consultation with cardiologist will be performed. The investigator has the final decision on the clinical significance of the ECG results.
EEG
An EEG is an electrophysiological monitoring method that records the electrical activity and measures voltage fluctuations resulting from ionic current within the neurons of the brain. In clinical contexts, EEG refers to the recording of the brain's spontaneous electrical activity over a period of time.
Blood and urine collection
safety blood tests - hematology\\blood count and biochemistry standard blood tests urinalysis - urine test analysis
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patient did not respond to at least 2 AED's therapy given in adequate doses;
* Patients current therapy is considered inadequate (not completely controlled by AEDs); patients had four or more countable seizures with a motor component per 4 week period;
* Patient is aged 1 year - 18 years inclusive at screening age;
* Patient took one or more AEDs treatment at dose which has been stable for at least 4 weeks before enrolment;
* Females of childbearing potential can only participate in the study if willing to use acceptable, effective methods of contraception during the trial and for three month after end of trial participation as defined in point 7.10 of this protocol;
* Patient/parent is able to read/understand informed consent.
* Male patients must either be surgically sterile or he and his female spouse/partner who is of childbearing potential must be willing to use highly effective methods of contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the study.
* All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation (VNS) were stable for four weeks prior to screening and participants were willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments are not counted as an AED.
Exclusion Criteria
* Known history or presence of serious cardiovascular disease
* Known or suspected history or family history of: schizophrenia, or other psychotic illness, severe personality disorder or other significant psychiatric disorder.
* Known or suspected allergy hypersensitivity or idiosyncratic reaction to cannabinoids or any other drug substances with similar activity or to any of the excipients of the IMP.
* Participant has clinically relevant abnormalities in the 12-lead electrocardiogram measured at screening or randomisation.
* Patients were currently using or had in the past used recreational or medicinal cannabis or synthetic CBD based medications or preparations within last 3 months or had previous or current treatment with cannabis-based therapy within last 3 months.
* History of drug or alcohol addiction requiring treatment.
* History of malabsorption within the last year or presence of clinically significant gastrointestinal disease or surgery that may affect drug bioavailability, including but not limited to cholecystectomy.
* Presence of hepatic or renal dysfunction.
* Females who: are pregnant (serum hCG level consistent with pregnancy diagnosis); or are lactating;
* Participation in a clinical trial that involved administration of an investigational medicinal product within 90 days prior to drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results;
* Participant has clinically significant abnormal laboratory values (e.g. liver enzymes);
* Participant has clinically significant findings from a physical examination (fever);
* In case of ketogenic diet or VNS; the diet need to be stable for at least 4 weeks, and VNS ramping needs to be stable at least 12 weeks before enrolment.
1 Year
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
MGC Pharmaceuticals d.o.o
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Rubi Zomer
Role: STUDY_DIRECTOR
MGC Pharmacuticals
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Schneider Children's Medical Center of Israel
Petach Tikvah, Central District, Israel
University Children's Hospital Ljubljana University Medical Centre Ljubljana
Ljubljana, , Slovenia
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Berg AT, Zelko FA, Levy SR, Testa FM. Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes: a prospective cohort study. Neurology. 2012 Sep 25;79(13):1384-91. doi: 10.1212/WNL.0b013e31826c1b55. Epub 2012 Sep 12.
Devinsky O, Vickrey BG, Cramer J, Perrine K, Hermann B, Meador K, Hays RD. Development of the quality of life in epilepsy inventory. Epilepsia. 1995 Nov;36(11):1089-104. doi: 10.1111/j.1528-1157.1995.tb00467.x.
Donner EJ. Opportunity gained, opportunity lost: treating pharmacoresistant epilepsy in children. Epilepsia. 2013 May;54 Suppl 2:16-8. doi: 10.1111/epi.12178.
Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia. 2014 Jun;55(6):787-90. doi: 10.1111/epi.12635. Epub 2014 May 22.
Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia. 2014 Jun;55(6):783-6. doi: 10.1111/epi.12610. Epub 2014 May 22.
Sharp GB, Samanta D, Willis E. Options for pharmacoresistant epilepsy in children: when medications don't work. Pediatr Ann. 2015 Feb;44(2):e43-8. doi: 10.3928/00904481-20150203-11.
Bent S. Herbal medicine in the United States: review of efficacy, safety, and regulation: grand rounds at University of California, San Francisco Medical Center. J Gen Intern Med. 2008 Jun;23(6):854-9. doi: 10.1007/s11606-008-0632-y. Epub 2008 Apr 16.
Russo EB. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers. 2007 Aug;4(8):1614-48. doi: 10.1002/cbdv.200790144.
Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimaraes FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006 Apr;39(4):421-9. doi: 10.1590/s0100-879x2006000400001. Epub 2006 Apr 3.
Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, Cilio MR. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8. doi: 10.1016/S1474-4422(15)00379-8. Epub 2015 Dec 24.
Cortesi M, Fusar-Poli P. Potential therapeutical effects of cannabidiol in children with pharmacoresistant epilepsy. Med Hypotheses. 2007;68(4):920-1. doi: 10.1016/j.mehy.2006.09.030. Epub 2006 Nov 16. No abstract available.
Dan B. Cannabinoids in paediatric neurology. Dev Med Child Neurol. 2015 Nov;57(11):984. doi: 10.1111/dmcn.12926. No abstract available.
Press CA, Knupp KG, Chapman KE. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015 Apr;45:49-52. doi: 10.1016/j.yebeh.2015.02.043. Epub 2015 Apr 3.
Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, Katz R, Di Marzo V, Jutras-Aswad D, Notcutt WG, Martinez-Orgado J, Robson PJ, Rohrback BG, Thiele E, Whalley B, Friedman D. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014 Jun;55(6):791-802. doi: 10.1111/epi.12631. Epub 2014 May 22.
Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49. doi: 10.2174/157488611798280924.
Koppel BS, Brust JC, Fife T, Bronstein J, Youssof S, Gronseth G, Gloss D. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders [RETIRED]: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Apr 29;82(17):1556-63. doi: 10.1212/WNL.0000000000000363.
Izquierdo I, Tannhauser M. Letter: The effect of cannabidiol on maximal electroshock seizures in rats. J Pharm Pharmacol. 1973 Nov;25(11):916-7. doi: 10.1111/j.2042-7158.1973.tb09976.x. No abstract available.
Chesher GB, Jackson DM, Malor RM. Interaction of delta9-tetrahydrocannabinol and cannabidiol with phenobarbitone in protecting mice from electrically induced convulsions. J Pharm Pharmacol. 1975 Aug;27(8):608-9. doi: 10.1111/j.2042-7158.1975.tb09515.x. No abstract available.
Jones NA, Hill AJ, Smith I, Bevan SA, Williams CM, Whalley BJ, Stephens GJ. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharmacol Exp Ther. 2010 Feb;332(2):569-77. doi: 10.1124/jpet.109.159145. Epub 2009 Nov 11.
Mula M. Investigational new drugs for focal epilepsy. Expert Opin Investig Drugs. 2016;25(1):1-5. doi: 10.1517/13543784.2016.1110144. Epub 2015 Nov 4.
Hess EJ, Moody KA, Geffrey AL, Pollack SF, Skirvin LA, Bruno PL, Paolini JL, Thiele EA. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia. 2016 Oct;57(10):1617-1624. doi: 10.1111/epi.13499. Epub 2016 Oct 3.
Tzadok M, Uliel-Siboni S, Linder I, Kramer U, Epstein O, Menascu S, Nissenkorn A, Yosef OB, Hyman E, Granot D, Dor M, Lerman-Sagie T, Ben-Zeev B. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure. 2016 Feb;35:41-4. doi: 10.1016/j.seizure.2016.01.004. Epub 2016 Jan 6.
Goldstein B. Cannabis in the treatment of pediatric epilepsy. O'Shaugnessy's 2016:7-9.
Reddy DS, Golub VM. The Pharmacological Basis of Cannabis Therapy for Epilepsy. J Pharmacol Exp Ther. 2016 Apr;357(1):45-55. doi: 10.1124/jpet.115.230151. Epub 2016 Jan 19.
Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015 Aug;56(8):1246-51. doi: 10.1111/epi.13060. Epub 2015 Jun 26.
O'Connell BK, Gloss D, Devinsky O. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav. 2017 May;70(Pt B):341-348. doi: 10.1016/j.yebeh.2016.11.012. Epub 2017 Feb 8.
Goodwin SW, Lambrinos AI, Ferro MA, Sabaz M, Speechley KN. Development and assessment of a shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Epilepsia. 2015 Jun;56(6):864-72. doi: 10.1111/epi.13000. Epub 2015 Apr 25.
Conway L, Widjaja E, Smith ML, Speechley KN, Ferro MA. Validating the shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) in a sample of children with drug-resistant epilepsy. Epilepsia. 2017 Apr;58(4):646-656. doi: 10.1111/epi.13697. Epub 2017 Feb 15.
Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007 Jul;4(7):28-37.
Bornheim LM, Everhart ET, Li J, Correia MA. Induction and genetic regulation of mouse hepatic cytochrome P450 by cannabidiol. Biochem Pharmacol. 1994 Jul 5;48(1):161-71. doi: 10.1016/0006-2952(94)90236-4.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.
Mortati K, Dworetzky B, Devinsky O. Marijuana: an effective antiepileptic treatment in partial epilepsy? A case report and review of the literature. Rev Neurol Dis. 2007 Spring;4(2):103-6.
Volkow ND, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014 Aug 28;371(9):879. doi: 10.1056/NEJMc1407928. No abstract available.
Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013 Dec;29(3):574-7. doi: 10.1016/j.yebeh.2013.08.037.
Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2012 Jun 13;(6):CD009270. doi: 10.1002/14651858.CD009270.pub2.
Zaccara G, Giovannelli F, Schmidt D. Placebo and nocebo responses in drug trials of epilepsy. Epilepsy Behav. 2015 Feb;43:128-34. doi: 10.1016/j.yebeh.2014.12.004. Epub 2015 Feb 19.
Sativex smpc , 20.09.2018
Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther. 1983 Sep;34(3):352-63. doi: 10.1038/clpt.1983.179.
Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther. 1980 Sep;28(3):409-16. doi: 10.1038/clpt.1980.181.
Related Links
Access external resources that provide additional context or updates about the study.
nice.org-( dne: 14.februarja 2016)
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
MGC-002
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.