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

• ClinicalTrials.gov Identifier: NCT02318602
• Recruitment Status: Completed
• First Posted: December 17, 2014
• Results First Posted: July 26, 2018
• Last Update Posted: July 26, 2018
• Sponsor: INSYS Therapeutics Inc
• Information provided by (Responsible Party): INSYS Therapeutics Inc

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).

Condition or disease	Intervention/treatment	Phase
Seizures	Drug: Cannabidiol Oral Solution	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 8, 2016
• Actual Primary Completion Date: June 22, 2017
• Actual Study Completion Date: June 22, 2017

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Adverse Events [ Time Frame: Up to Week 50 ]
   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.
2. Percentage of Participants With Serious Adverse Events [ Time Frame: Up to Week 50 ]
   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.
3. Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values [ Time Frame: Up to Week 50 ]
   Laboratory values include chemistry and hematology, and urinary analysis.
4. Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings [ Time Frame: Up to Week 48 ]
5. Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Up to Week 50 ]
6. Change From Baseline in Trough Plasma Levels of Cannabidiol and Its 7-OH Metabolite [ Time Frame: Up to Week 50 ]

Secondary Outcome Measures :

1. Vineland Adaptive Behavior Scales (VABS) [ Time Frame: Up to Week 48 ]

   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.

2. Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to Week 50 ]
   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.

Other Outcome Measures:

1. Clinical Global Impression of Severity (CGI-S) [ Time Frame: through study completion, up to 48 weeks or marketing approval, whichever is earlier ]

   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.

2. Impact of Pediatric Epilepsy Scale (IPES) [ Time Frame: through study completion, up to 48 weeks or marketing approval, whichever is earlier ]

   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.

3. Clinical Global Impression of Improvement (CGI-I) [ Time Frame: through study completion, up to 48 weeks or marketing approval, whichever is earlier ]

   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.

4. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

  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

Contacts and Locations

Locations

United States, California

University of California San Francisco Medical Center

San Francisco, California, United States, 94143

United States, Florida

Miami Children's Hospital

Miami, Florida, United States, 33155

Child Neurology Center - NW F

Pensacola, Florida, United States, 32504

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Nevada

Clinical Research Center of Nevada LLC

Las Vegas, Nevada, United States, 89104

United States, Oregon

Oregon Health Services University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Le Bonheur Children's Hospital

Memphis, Tennessee, United States, 38103

United States, Texas

Texas Scottish Rite Hospital for Children

Dallas, Texas, United States, 79219

United States, Utah

Granger Medical Clinic

Riverton, Utah, United States, 84096

United States, Washington

Mary Bridge Children's Hospital

Tacoma, Washington, United States, 98403

Sponsors and Collaborators

INSYS Therapeutics Inc

Investigators

• Study Director: Neha Parikh; INSYS Therapeutics Inc

  Study Documents (Full-Text)

Documents provided by INSYS Therapeutics Inc:

Study Protocol  [PDF] March 6, 2017

Statistical Analysis Plan  [PDF] December 4, 2017

More Information

• Responsible Party: INSYS Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT02318602
• Other Study ID Numbers: INS011-14-030
• First Posted: December 17, 2014
• Results First Posted: July 26, 2018
• Last Update Posted: July 26, 2018
• Last Verified: June 2018

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

Keywords provided by INSYS Therapeutics Inc:

Lennox-Gastaut syndrome; Dravet syndrome; Treatment-resistant seizures

Additional relevant MeSH terms:

Seizures; Epilepsy; Neurologic Manifestations; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Cannabidiol; Anticonvulsants