University of Alabama at Birmingham (UAB) Pediatric CBD Program

NCT02695537 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: IRB-140905010
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of Epidiolex at various doses between 5 mg/kg/day and 50 mg/kg/day as an additional (add-on) drug for treating debilitating, drug-resistant epilepsy.

Conditions

Epilepsy; Seizures

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Severe Adverse Events (Increase in Seizure Frequency by More Than 100% Leading to Emergency Room Visit or Hospitalization).

  Severe adverse events (SAEs) were defined as increase in seizure frequency by more than 100% leading to emergency room visit or hospitalization. During study clinic and phone visits, adverse and severe adverse event monitoring and reporting were assessed among all participants. Data was recorded and stored in the UAB RedCap System.

  For 1 Year following Enrollment

• Number of Participants With Change in Resting Blood Pressure or Heart Rate by 25% if Considered Significant by Managing Neurologist.

  During study clinic visits, participant vital signs, including blood pressure and heart rate, were collected. Data was recorded and stored in the UAB RedCap System. Clinically significant was determined by using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Adverse events categorized as a grade 3 or above were considered clinically significant. Adverse events grade 4 or above were considered severe adverse events.

  For 1 Year following Enrollment

• Number of Participants With Change in Laboratory Tests Considered by Managing Neurologists as Clinically Significant.

  During study clinic visits, participants received laboratory testing to assess for side effects and toxicity. Data was recorded and stored in the UAB RedCap System. Laboratory testing included Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP; included Liver Function Tests (LFTs) mainly looking at alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), Urine Analysis (UA), and Antiepileptic Drug (AED) levels. Clinically significant was determined by using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Adverse events categorized as a grade 3 or above were considered clinically significant. Adverse events grade 4 or above were considered severe adverse events.

  For 1 Year following Enrollment

Secondary Outcomes (2)

• Change in Seizure Frequency as Measured in Total Number of Seizures Per Month.

  For 1 Year following Enrollment

• Change in Seizure Severity Measured by the Chalfont Seizure Severity Scale (Duncan & Sander, 1991, JNNP).

  For 1 Year following Enrollment

Study Arms (1)

Epidiolex 100 milligram/milliliter (mg/mL) oral solution

EXPERIMENTAL

Participants will receive a CBD starting dose of 5 mg/kg/day in twice daily dosing and titrate by 5 mg/kg/2 weeks up to 25 mg/kg/day. Additional increases in dosing, by 5 mg/kg/day up to a maximum of 50 mg/kg/day, may be instituted at the discretion of the treating Principle Investigator (PI). If a subject experiences a "clinically significant" or "dose limiting" adverse event (AE) or severe adverse event (SAE) attributable to CBD, the investigator will determine if a dose reduction or taper is necessary (decreases will occur in 5 mg/kg/2 week increments or at a rate felt appropriate by the treating PI).

Drug: Epidiolex

Interventions

Epidiolex DRUG

Epidiolex oral solution (100 mg/mL CBD concentration) with inactive ingredients including anhydrous ethanol, sesame seed oil, strawberry flavor, and sucralose).

Also known as: Cannabidiol, CBD

Epidiolex 100 milligram/milliliter (mg/mL) oral solution

Eligibility Criteria

• Age: 1 Year - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients between 1 years (12 months)-18 years with drug resistant epilepsy confirmed by video EEG recording report, and
• Patient should have history of a trial of at least four anti-epileptic drugs (AEDs), including one trial of a combination of two concomitant drugs without successful seizure control. Vagal nerve stimulation (VNS), Responsive Neurostimulation (RNS) deep brain stimulation, or the ketogenic diet can be considered equivalent to a drug trial. Patient suffering from an epileptic syndrome that is known to be refractory to treatment, such as Dravet or Lennox-Gastaut Syndrome, may be included after a trial of only two drugs, and
• Between 1-4 baseline anti-epileptic drugs at stable doses for a minimum of 4 weeks prior to submitting records for review by the CBD Treatment Approval Committee.
• VNS or RNS must be on stable settings for a minimum of 3 months.
• If on ketogenic diet, must be on stable ration for a minimum of 3 months.
• Review of the following patient medical information:
• Most recent Brain MRI report,
• Most recent ECG report,
• Video/EEG monitoring report confirming the diagnosis of epilepsy,
• Evidence that the patient has failed 4 AEDs as indicated above,
• Patient must have at least 4 clinically countable seizures per month,
• Seizure history to include a documented history of generalized (drop, atonic, tonic clonic, and/or myoclonic) seizures, focal seizures without loss of consciousness with a motor component, focal seizures with loss of consciousness, or focal seizures with secondary generalization, complex partial seizures with a motor or tonic component, and I or altered awareness seizures,
• Results of routine testing including blood work (Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), Liver Function Tests (LFTs), renal panel, Urinary Analysis (UA), and levels of all AEDs) and digital copy of a routine EEG along with the formal written report performed within 3 months prior to submitting records for CBD Treatment Approval review. If applicable, results of any metabolic or genetic testing performed should be included in submitted records for review. If any AED dose was adjusted in the preceding 3 months, level on the new dose will need to be provided.
• If applicable, documentation (including date of surgery) of prior VNS, RNS, Corpus Callosotomy, or other epilepsy surgery the patient has received.
• Acceptable method of contraception (or abstinence) for women of childbearing potential and for male patients with partners of childbearing potential, and female patients must have a negative urine pregnancy test on the day of initiating CBD.

You may not qualify if:

• Active Psychogenic non-epileptic seizures (PNES); Patients with more than 1 year freedom from PNES will not be excluded,
• Patients who are pregnant, breastfeeding, or not using acceptable methods of contraception during the course of the study and for three months thereafter,
• Male patient's partner is of child bearing potential; unless willing to ensure that they (male patients) or their partner(s) are using acceptable methods of contraception during the course of the study and for three months thereafter
• History of substance abuse/addiction,
• Use of medical marijuana or CBD based product in the past 30 days,
• Initiation of felbamate within last 12 months,
• Allergy to CBD or any marijuana-type products,
• Alanine Aminotransferase (ALT) \>5 x Upper Limit of Normal (ULN) or Aspartate Aminotransferase (AST) \>5 x ULN, as seen in participant's laboratory results submitted to the CBD Treatment Approval Committee for review.
• Hemoglobin \<10 or Hematocrit \<30 or White Blood Cell (WBC) \< 2000, as seen in participant's laboratory results submitted to the CBD Treatment Approval Committee for review.
• In Investigator's judgement, active medical condition/treatment that impacts study activities.
• Unable to provide consent (and no LAR),
• Unable/Failure to comply with study visits/requirements and/or instructions.
• Confirmed diagnosis for Dravet Syndrome or Lennox-Gastaut Syndrome that qualifies the patient for a Greenwich (GW) Dravet Syndrome or Lennox-Gastaut Syndrome randomized controlled clinical trial for which the patient is eligible pursuant to the GW clinical trial enrollment criteria unless
• (a) there is no study that is either actively open for enrollment of patients at The University of Alabama at Birmingham (UAB) or that is expected to actively begin enrolling patients at UAB within two (2) months of the date on which the patient is screened for the UAB Pediatric CBD Program or UAB Adult CBD Program. Primary residence in a State different than Alabama.
• Subjects with contraindications to MRI/fMRI at 3 Tesla (e.g., metallic artifact) will not be offered participation in the optional sub-study.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Related Publications (4)

• Duncan JS, Sander JW. The Chalfont Seizure Severity Scale. J Neurol Neurosurg Psychiatry. 1991 Oct;54(10):873-6. doi: 10.1136/jnnp.54.10.873.

  PMID: 1744641 BACKGROUND

• Pinheiro, J.C. and Bates, D.M. (2000). Mixed-Effects Models in S and S-Plus. Springer, Verlag, New York

  BACKGROUND

• Szaflarski JP, Hernando K, Bebin EM, Gaston TE, Grayson LE, Ampah SB, Moreadith R. Higher cannabidiol plasma levels are associated with better seizure response following treatment with a pharmaceutical grade cannabidiol. Epilepsy Behav. 2019 Jun;95:131-136. doi: 10.1016/j.yebeh.2019.03.042. Epub 2019 Apr 29.

  PMID: 31048098 DERIVED

• Warren PP, Bebin EM, Nabors LB, Szaflarski JP. The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy. Neurocase. 2017 Oct-Dec;23(5-6):287-291. doi: 10.1080/13554794.2017.1391294. Epub 2017 Oct 24.

  PMID: 29063814 DERIVED

Related Links

• UAB Cannabidiol Program

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Flexible dosing schedule; Over- or underreporting of seizure frequency and severity that may reflect patients' or caregivers' desires to qualify or remain in the study; Non-normality of the data; Early withdrawal of participants.

Results Point of Contact

• Title: Dr. Martina Bebin, MD
• Organization: University of Alabama at Birmingham

ebebin@uab.edu

205-934-3866

Study Officials

• Martina Bebin, MD

  Neurology Chair Office - University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 1, 2016
• Study Start: April 1, 2015
• Primary Completion: February 27, 2019
• Study Completion: February 27, 2019
• Last Updated: April 10, 2020
• Results First Posted: April 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)