Cannabidiol Oral Solution as an Adjunctive Treatment for Treatment-resistant Seizure Disorder

A Multicenter, Open-label, Flexible Dose Study to Assess the Long-term Safety of Pharmaceutical Cannabidiol Oral Solution as an Adjunctive Treatment for Pediatric Subjects With a Treatment-resistant Seizure Disorder Who Complete INS011-14-029 or Part A of INS011-15-054

This is a multicenter, open-label trial to assess the long-term safety and efficacy of Cannabidiol Oral Solution as adjunctive therapy for pediatric participants with treatment-resistant seizure disorders, including Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS). All participants have rolled over from previous trials: INS011-14-029 (NCT02324673) and INS011-15-054 (NCT02551731).

Study Overview

• Status: Completed
• Conditions: Seizures
• Intervention / Treatment: Drug: Cannabidiol Oral Solution

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Pensacola, Florida, United States, 32504
      • Child Neurology Center - NW F
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Clinical Research Center of Nevada LLC
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Services University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Le Bonheur Children's Hospital
  • Texas
    • Dallas, Texas, United States, 79219
      • Texas Scottish Rite Hospital for Children
  • Utah
    • Riverton, Utah, United States, 84096
      • Granger Medical Clinic
  • Washington
    • Tacoma, Washington, United States, 98403
      • Mary Bridge Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Completed activities through Day 11 in INS011-14-029 or Part A (Visit 6) INS011-15-054
• Informed consent/assent (as applicable) was voluntarily provided by the participant and/or parent(s)/caregiver(s) in accordance with applicable laws, regulations, and local requirements
• Is medically stable with no anticipated changes in chronic medications in the opinion of the Investigator
• Continues to meet protocol-specified criteria for qualification and contraception, including treatment-resistant seizure disorder
• In the opinion of the Investigator, the subject and/or parent(s)/caregiver(s) are able to continue keeping accurate seizure diaries

Exclusion Criteria:

• Inadequate supervision by parent(s)/caregiver(s)
• History or current use of dietary supplements, drugs or over-the counter medications outside protocol-specified parameters

• Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
  3. the analysis of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infants; Participants 1 to<2 years of age. Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The maximum daily dose was 40 mg/kg/day. Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The total daily dose, milligrams per kilograms per day (mg/kg/day), will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion.	Drug: Cannabidiol Oral Solution; An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Experimental: Children; Participants 2 to <12 years of age. Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.The maximum daily dose was 40 mg/kg/day. Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The total daily dose (mg/kg/day) will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion.	Drug: Cannabidiol Oral Solution; An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Experimental: Adolescents; Participants 12 to <17 years of age. Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The maximum daily dose was 40 mg/kg/day. Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The total daily dose (mg/kg/day) will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion.	Drug: Cannabidiol Oral Solution; An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	An Adverse Event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product. It does not necessarily have a causal relationship with this treatment.	Up to Week 50
Percentage of Participants With Serious Adverse Events	A serious adverse event is any untoward medical occurrence ( whether considered to be related to investigational product or not) that at any dose results in death, is life threatening, requires inpatient hospitalization, results in disability/incapacity, is a congenital abnormality/ birth defect, or medically significant as determined by an investigator.	Up to Week 50
Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values	Laboratory values include chemistry and hematology, and urinary analysis.	Up to Week 50
Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings		Up to Week 48
Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs		Up to Week 50
Change From Baseline in Trough Plasma Levels of Cannabidiol and Its 7-OH Metabolite		Up to Week 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vineland Adaptive Behavior Scales (VABS)	The Vineland Adaptive Behavior Scales measures the personal and social skills of individuals from birth through adulthood. Because adaptive behavior refers to an individual's typical performance of the day-to-day activities required for personal and social sufficiency, these scales assess what a person actually does, rather than what he or she is able to do. The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. The 4 domains are Communication, Daily Living Skills, Motor Skills, and Maladaptive Behaviour Index. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. A rise in standard scores from Baseline indicates improvement. The VABS will be completed for all participants.	Up to Week 48
Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS)	For subjects 7 years of developmental age or older, the Columbia-Suicide Severity Rating Scale (C-SSRS) will be administered to access suicidality. The appropriate adult version will be used in subjects 12 years of (developmental) age and older. The investigator will determine the participant's developmental age.	Up to Week 50

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression of Severity (CGI-S)	The severity of the participant's illness is rated on a seven-point scale, where 1=normal, not at all ill, and 7=among the most extremely ill patients. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. The score reflects the average severity level across the seven days. The CGI-S will be completed for all participants, regardless of chronological and developmental age.	through study completion, up to 48 weeks or marketing approval, whichever is earlier
Impact of Pediatric Epilepsy Scale (IPES)	The IPES assesses the impact on academic achievement, participation in activities, health, relationships with family and with peers and siblings, social activities, self-esteem, and the caregiver's hopes for their child's future. It takes about 3 minutes for the parent to complete. Each of the 11 items is given a severity score of 0 (not at all) to 3 (a lot). The higher the score, the higher is the impact of epilepsy on that item. The highest total score possible is 33 (range 0-33). The Impact of Pediatric Epilepsy Scale (IPES) is validated for subjects who are 2 to 16 years of age. Due to developmental delay characteristic of the study population, subjects through 18 years of chronological age will complete the IPES. Subjects over 18 years of chronological age will not complete the IPES.	through study completion, up to 48 weeks or marketing approval, whichever is earlier
Clinical Global Impression of Improvement (CGI-I)	The participant's overall clinical condition is compared to the one week period just before the start of medication (the baseline visit). The participant's condition is compared to the patient's condition at admission to the project [prior to starting treatment] on a 7-point scale, where 1=very much improved since the initiation of treatment; and 7=very much worse since the initiation of treatment. The CGI-I will be completed for all participants, regardless of chronological and developmental age.	through study completion, up to 48 weeks or marketing approval, whichever is earlier
Change From Baseline in Frequency of Seizures as a Measure of Seizure Control		through study completion, up to 48 weeks or marketing approval, whichever is earlier

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc
• Investigators: Study Director: Neha Parikh, INSYS Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2016
• Primary Completion (Actual): June 22, 2017
• Study Completion (Actual): June 22, 2017

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 16, 2014
• First Posted (Estimate): December 17, 2014

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Treatment-resistant seizures; Dravet syndrome; Lennox-Gastaut syndrome
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: INS011-14-030

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No