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Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Childhood Absence Seizures

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ClinicalTrials.gov Identifier: NCT03336242
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
INSYS Therapeutics Inc

Brief Summary:
The primary purpose of this study is to assess the efficacy of Cannabidiol Oral Solution in the treatment of pediatric participants with treatment-resistant childhood absence seizures. This study will also assess safety, tolerability and pharmacokinetics of Cannabidiol Oral Solution, and any improvement in qualitative assessments of participant status over the duration of the study in pediatric participants with treatment-resistant childhood absence seizures. The study will include a 4-week Screening Period, a 5 or 10 day Titration Period (depending study Cohort), a 4-week Treatment Period followed by 5-day Tapering for doses >20 mg/kg/day and a 4-week Follow-up Period.

Condition or disease Intervention/treatment Phase
Childhood Absence Epilepsy Drug: Cannabidiol Oral Solution Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Dose-finding Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Pharmaceutical Grade Synthetic Cannabidiol Oral Solution in Pediatric Patients With Treatment-Resistant Childhood Absence Seizures
Actual Study Start Date : December 15, 2017
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2019


Arm Intervention/treatment
Experimental: Cohort 1: Cannabidiol Oral Solution 20 mg/kg/day
Treatment Period: Cannabidiol Oral Solution 20 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) for 4 weeks.
Drug: Cannabidiol Oral Solution
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Experimental: Cohort 2: Cannabidiol Oral Solution 30 mg/kg/day

Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days.

Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks.

Drug: Cannabidiol Oral Solution
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Experimental: Cohort 3: Cannabidiol Oral Solution 40 mg/kg/day

Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days, followed by 30 mg/kg/day divided BID for 5 days.

Treatment Period: Cannabidiol Oral Solution 40 mg/kg/day divided BID for 4 weeks.

Drug: Cannabidiol Oral Solution
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).




Primary Outcome Measures :
  1. Percent Change from Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5 [ Time Frame: Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period) ]
    A 4-hour video-EEG will be performed for all participants at Baseline, during the Treatment Period, and at the End of Study/Early Withdrawal Visit. Hyperventilation will be conducted during the video-EEG to count the number of absence seizures.

  2. Percent Change from Baseline in Time to Absence Seizure During Hyperventilation Testing on Video-EEG at Visit 5 [ Time Frame: Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period) ]
    A 4-hour video-EEG will be performed for all participants at Baseline, during the Treatment Period, and at the End of Study/Early Withdrawal Visit. Hyperventilation will be conducted during the video-EEG to count the number of absence seizures.

  3. Percentage of Participants Seizure-Free at Visit 5 [ Time Frame: Screening (Visit 1, Day -28 to -1 of Screening Period) Up to Visit 5 (Week 4, Day 6 of Treatment Period ]
    Daily seizure activity will be recorded in a diary. Each day, the patient or parent/caregiver will respond to the question: "How many absence seizures did the patient have today?".

  4. Clinical Global Impression of Improvement (CGI-I) Score at Visit 5 [ Time Frame: Visit 5 (Week 4, Day 6 of Treatment Period) ]
    The CGI-I will be completed by the parents/caregivers and the investigator and will be used to assess participants global status of their condition at Week 4 of the Treatment Period using a 7-point scale, where 1=very much improved and 7=very much worse since the initiation of treatment.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Screening (Visit 1, Day -28 to -1 of Screening Period) up to Visit 7 (Week 4 of the Follow-Up Period) ]
    An AE is defined as any untoward medical occurrence in a patient administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A TEAE is an AE with onset that occurs after receiving study drug. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires the participant be at a risk of death at the time of the event, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, or other serious event that requires medical or surgical intervention.

  2. Change from Baseline in Vital Signs During the Treatment Period [ Time Frame: Baseline (Visit 2, Day 1 of Titration period) and Visit 6 (Week 4, Day 7 of Treatment period) ]
  3. Change from Screening in Laboratory Values During the Treatment Period [ Time Frame: Screening (Visit 1, Day -28 to -1 of Screening period) and Visit 6 (Week 4, Day 7 of Treatment period) ]
  4. Maximum Plasma Concentration (Cmax) and Dose-normalized Cmax (Cmax/D) for Cannabidiol Under Fed and Fasted Conditions [ Time Frame: Visit 3 (Week 1, Day 1 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), Visit 5 (Week 4, Day 6 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), and Visit 6 (Week 4, Day 7 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose) ]

    Fed: Patient will arrive at the site on Day 1 of Week 4 of the Treatment Period without food and the morning dose. Site will provide a high fat/high calorie food then doses patient. Blood samples will be collected pre-dose (before meal/morning dose) and 2, 4, 6 hours after the morning dose (but before next dose).

    Fasted (2 hours before dose until 2 hours after dose): Patients will arrive at the site on Day 2 of Week 4 of the Treatment Period without food and the morning dose. Site will provide a standard meal 2 hours after dose. Blood samples will be collected pre-dose and 2 (before meal), 4, 6 hours after the morning dose (but before next dose).


  5. Area Under the Plasma Concentration Curve from Time 0 to the Last Measured Concentration (AUC(0-t)) and Dose Normalized AUC(0-t) [AUC(0-t)/Dose] for Cannabidiol Under Fed and Fasted Conditions [ Time Frame: Visit 3 (Week 1, Day 1 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), Visit 5 (Week 4, Day 6 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), and Visit 6 (Week 4, Day 7 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose) ]

    Fed: Patient will arrive at the site on Day 1 of Week 4 of the Treatment Period without food and the morning dose. Site will provide a high fat/high calorie food then doses patient. Blood samples will be collected pre-dose (before meal/morning dose) and 2, 4, 6 hours after the morning dose (but before next dose).

    Fasted (2 hours before dose until 2 hours after dose): Patients will arrive at the site on Day 2 of Week 4 of the Treatment Period without food and the morning dose. Site will provide a standard meal 2 hours after dose. Blood samples will be collected pre-dose and 2 (before meal), 4, 6 hours after the morning dose (but before next dose).


  6. Trough Plasma Concentration (Ctrough) and Dose normalized Ctrough (Ctrough/Dose) for Cannabidiol Under Fed, Fasted and Normal Conditions [ Time Frame: Visit 3 (Week 1, Day 1 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), Visit 5 (Week 4, Day 6 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), and Visit 6 (Week 4, Day 7 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose) ]

    Fed: Patient will arrive at the site on Day 1 of Week 4 of the Treatment Period without food and the morning dose. Site will provide a high fat/high calorie food then doses patient. Blood samples will be collected pre-dose (before meal/morning dose) and 2, 4, 6 hours after the morning dose (but before next dose).

    Fasted (2 hours before dose until 2 hours after dose): Patients will arrive at the site on Day 2 of Week 4 of the Treatment Period without food and the morning dose. Site will provide a standard meal 2 hours after dose. Blood samples will be collected pre-dose and 2 (before meal), 4, 6 hours after the morning dose (but before next dose).

    Under normal condition blood samples will be collected pre-dose.




Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient and/or parent(s)/caregiver(s) fully comprehend the informed consent form (ICF) and assent form, understand all study procedures, and can communicate satisfactorily with the investigator and study coordinator, in accordance with applicable laws, regulations, and local requirements.
  2. Male or female between 3 and 12 years (inclusive) at the time of onset and between 3 and 17 years of age (inclusive) at the time of consent.
  3. Body weight ≥ 10 kg.
  4. Diagnosed with childhood absence epilepsy (CAE), confirmed by electroencephalogram (EEG), with ≥ 5 absence seizures during the 4-hour EEG with treatment-resistant absence seizures, and has had an adequate trial of at least 2 anti-epileptic drugs (AED)s and are treatment-resistant to at least one AED.
  5. Willingness to not start a ketogenic diet during the Baseline or Treatment Period.
  6. Have on average ≥ 5 absence seizures per day.
  7. A female patient is eligible to participate in the study if she is premenarchal, or of childbearing potential with a negative urine pregnancy test at the Screening Visit. If sexually active, she must agree to either complete abstinence from intercourse or use acceptable methods of contraception throughout the study and for 4 weeks after completion of study participation or discontinuation from investigational product.
  8. A sexually active male patient must be willing to use acceptable methods of contraception throughout the study and for 4 weeks after completion of study participation or discontinuation from investigational product.
  9. In the opinion of the investigator, the parent(s)/caregiver(s) is willing and able to comply with the study procedures and visit schedules and the Follow-up Visits.
  10. General good health based on physical and neurological examinations, medical history, and clinical laboratory values completed during the Screening Visit that would prohibit the patient from safely participating in the trial as judged by the investigator.

Exclusion Criteria:

  1. Patient or parent(s)/caregiver(s) have daily commitments during the study duration that would interfere with attending all study visits.
  2. Has a history of nonfebrile seizures other than absence seizures.
  3. Has a history of febrile seizures after 3 years of age.
  4. Has a history consistent with juvenile absence epilepsy or juvenile myoclonic epilepsy.
  5. Currently taking felbamate.
  6. Currently taking phenytoin, fluvoxamine, carbamazepine, or St. John's Wort.
  7. Currently taking concomitant medications that are strong inhibitors/inducers/sensitive substrates with a narrow therapeutic index for cytochrome P450 3A4 (CYP3A4), CYP2C9, or CYP2C19. (Stable doses of Valproic Acid during the screening, titration, treatment, and follow-up periods are permitted).
  8. Currently on a ketogenic diet.
  9. In the opinion of the investigator, any clinically significant, unstable medical abnormality, chronic disease, or a history of a clinically significant abnormality of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems.
  10. Clinically significant abnormal liver function test (LFT) values, including albumin, direct bilirubin, total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≥3 times the upper limit of normal (ULN).
  11. History or presence of abnormal electrocardiograms (ECGs) that are clinically significant in the opinion of the investigator.
  12. Has a current or history of clinically significant intellectual disability or major psychiatric disease, including autism spectrum disorder, which would interfere with compliance.
  13. For patients aged 7 to 17 years of age and for whom the Columbia Suicide Severity Rating Scale (C-SSRS) is developmentally appropriate, an affirmative answer to queries regarding active suicidal ideation with some intent to act but without a specific plan or active suicidal ideation with a specific plan and intent on the C-SSRS assessment at the Screening Visit.
  14. Any history of attempted suicide.
  15. Previously received any investigational drug or device or investigational therapy within 30 days before Screening.
  16. Taken any cannabinoids in the 30 days prior to the Screening Visit.
  17. History of an allergic reaction or a known or suspected sensitivity to any substance that is contained in the investigational product formulation.
  18. Known infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  19. In the opinion of the investigator, the patient is unsuitable in any other way to participate in this study.
  20. Body weight < 10 kg or > 80 kg.
  21. Patients who do not have at least 5 absence seizures on 4-hour video-EEG will be considered screen failures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03336242


Locations
United States, California
University of California San Francisco/ Benioff Children's Hospital Withdrawn
San Francisco, California, United States, 94143
United States, Florida
Nicklaus Children's Hospital Recruiting
Miami, Florida, United States, 33155
Contact: Research Coordinator    786-624-3516    tami.quintero@mch.com   
Pediatric Epilepsy and Neurology Specialists Recruiting
Tampa, Florida, United States, 33609
Contact: Research Coordinator    813-873-7367    mayra@pensresearch.org   
United States, Ohio
Akron Children's Hospital Recruiting
Akron, Ohio, United States, 44308
Contact: Research Coordinator    330-543-0690    jkatz@akronchildrens.org   
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Research Coordinator    503-494-8881    straussc@ohsu.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Research Coordinator    215-590-4136    minnick@email.chop.edu   
United States, Utah
Primary Children's Hospital Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Research Coordinator    801-587-1227    Andrew.Newton@hsc.utah.edu   
United States, Virginia
Children's Specialty Group, Division of Child & Adolescent Neurology Recruiting
Norfolk, Virginia, United States, 23510
Contact: Research Coordinator    757-668-9356    Terrie.Conklin@chkd.org   
United States, Washington
Research and Innovation/MultiCare Health System Recruiting
Tacoma, Washington, United States, 98405
Contact: Research Coordinator    253-403-9348    ccanorro@multicare.org   
Sponsors and Collaborators
INSYS Therapeutics Inc
Investigators
Study Director: Giovanni DeCastro INSYS Therapeutics Inc

Responsible Party: INSYS Therapeutics Inc
ClinicalTrials.gov Identifier: NCT03336242     History of Changes
Other Study ID Numbers: INS011-17-103
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Seizures
Epilepsy, Absence
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Epilepsy, Generalized
Pharmaceutical Solutions