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

Primary Purpose

Seizures

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cannabidiol Oral Solution
Sponsored by
INSYS Therapeutics Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Seizures focused on measuring Lennox-Gastaut syndrome, Dravet syndrome, Treatment-resistant seizures

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Francisco Medical Center
  • Miami Children's Hospital
  • Child Neurology Center - NW F
  • University of Chicago Medical Center
  • Clinical Research Center of Nevada LLC
  • Oregon Health Services University
  • Children's Hospital of Philadelphia
  • Le Bonheur Children's Hospital
  • Texas Scottish Rite Hospital for Children
  • Granger Medical Clinic
  • Mary Bridge Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Infants

Children

Adolescents

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values
Laboratory values include chemistry and hematology, and urinary analysis.
Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings
Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs
Change From Baseline in Trough Plasma Levels of Cannabidiol and Its 7-OH Metabolite

Secondary Outcome Measures

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.
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.

Full Information

First Posted
December 12, 2014
Last Updated
June 26, 2018
Sponsor
INSYS Therapeutics Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02318602
Brief Title
Cannabidiol Oral Solution as an Adjunctive Treatment for Treatment-resistant Seizure Disorder
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
January 8, 2016 (Actual)
Primary Completion Date
June 22, 2017 (Actual)
Study Completion Date
June 22, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
INSYS Therapeutics Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Seizures
Keywords
Lennox-Gastaut syndrome, Dravet syndrome, Treatment-resistant seizures

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Infants
Arm Type
Experimental
Arm Description
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.
Arm Title
Children
Arm Type
Experimental
Arm Description
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.
Arm Title
Adolescents
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cannabidiol Oral Solution
Intervention Description
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events
Description
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.
Time Frame
Up to Week 50
Title
Percentage of Participants With Serious Adverse Events
Description
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.
Time Frame
Up to Week 50
Title
Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values
Description
Laboratory values include chemistry and hematology, and urinary analysis.
Time Frame
Up to Week 50
Title
Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings
Time Frame
Up to Week 48
Title
Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame
Up to Week 50
Title
Change From Baseline in Trough Plasma Levels of Cannabidiol and Its 7-OH Metabolite
Time Frame
Up to Week 50
Secondary Outcome Measure Information:
Title
Vineland Adaptive Behavior Scales (VABS)
Description
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.
Time Frame
Up to Week 48
Title
Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
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.
Time Frame
Up to Week 50
Other Pre-specified Outcome Measures:
Title
Clinical Global Impression of Severity (CGI-S)
Description
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.
Time Frame
through study completion, up to 48 weeks or marketing approval, whichever is earlier
Title
Impact of Pediatric Epilepsy Scale (IPES)
Description
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.
Time Frame
through study completion, up to 48 weeks or marketing approval, whichever is earlier
Title
Clinical Global Impression of Improvement (CGI-I)
Description
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.
Time Frame
through study completion, up to 48 weeks or marketing approval, whichever is earlier
Title
Change From Baseline in Frequency of Seizures as a Measure of Seizure Control
Time Frame
through study completion, up to 48 weeks or marketing approval, whichever is earlier

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: the safety or well-being of the participant or study staff the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding) the analysis of results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neha Parikh
Organizational Affiliation
INSYS Therapeutics Inc
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Miami Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Child Neurology Center - NW F
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32504
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Clinical Research Center of Nevada LLC
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89104
Country
United States
Facility Name
Oregon Health Services University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Le Bonheur Children's Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Texas Scottish Rite Hospital for Children
City
Dallas
State/Province
Texas
ZIP/Postal Code
79219
Country
United States
Facility Name
Granger Medical Clinic
City
Riverton
State/Province
Utah
ZIP/Postal Code
84096
Country
United States
Facility Name
Mary Bridge Children's Hospital
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98403
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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