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

NCT03336242 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: INS011-17-103
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

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.

Conditions

Childhood Absence Epilepsy

Outcome Measures

Primary Outcomes (4)

• Percent Change From Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5

  A 4-hour video-EEG was performed for all participants at Baseline, during the Treatment Period, and at the End of the Study/Early Withdrawal Visit. Hyperventilation was conducted during the video-EEG to count the number of absence seizures. A negative change value indicates an improvement in seizure activity. A positive change value indicates a worsening in seizure activity. Percent change from baseline was calculated as (100\*(week 4-baseline)/baseline).

  Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)

• Percent Change From Baseline in Time to Absence Seizure During Hyperventilation Testing on Video-EEG at Visit 5

  A 4-hour video-EEG was performed for all participants at Baseline, during the Treatment Period, and at the End of the Study/Early Withdrawal Visit. Hyperventilation was conducted during the video-EEG to count the number of absence seizures. Percent change from baseline calculated as (100\*(week 4-baseline)/baseline).

  Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)

• Number of Participants Seizure-Free at Visit 5

  Daily seizure activity was recorded in a diary. Each day, the participant or parent/caregiver responded to the question: "How many absence seizures did the patient have today?".

  Visit 5 (Week 4, Day 6 of Treatment Period)

• Clinical Global Impression of Improvement (CGI-I) Score at Visit 5

  The CGI-I questionnaire was completed by the parents/caregivers and the investigator and was 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.

  Visit 5 (Week 4, Day 6 of Treatment Period)

Secondary Outcomes (4)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Day 1 (after dosing) up to Visit 7 (Week 4 of the Follow-Up Period)

• Maximum Plasma Concentration (Cmax) and Dose-normalized Cmax (Cmax/D) for Cannabidiol Under Fed and Fasted Conditions

  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)

• 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

  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)

• Trough Plasma Concentration (Ctrough) and Dose Normalized Ctrough (Ctrough/Dose) for Cannabidiol Under Fed, Fasted, and Normal Conditions

  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)

Study Arms (3)

Cohort 1: Cannabidiol Oral Solution 20 mg/kg/day

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Cohort 3: Cannabidiol Oral Solution 10 mg/kg/day

EXPERIMENTAL

Treatment Period: Cannabidiol Oral Solution 10 mg/kg/day divided BID for 4 weeks.

Drug: Cannabidiol Oral Solution

Interventions

Cannabidiol Oral Solution DRUG

An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Cohort 1: Cannabidiol Oral Solution 20 mg/kg/day; Cohort 2: Cannabidiol Oral Solution 30 mg/kg/day; Cohort 3: Cannabidiol Oral Solution 10 mg/kg/day

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patient and/or parent(s)/caregiver(s) fully comprehend the informed consent form 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.
• 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.
• Body weight ≥ 10 kg.
• Diagnosed with childhood absence epilepsy, confirmed by electroencephalogram (EEG) with at least 3 bursts of general spike wave of 2.7 to 5 hertz lasting ≥3 seconds during the 4-hour EEG, and has had an adequate trial of at least 2 antiepileptic drugs (AEDs) and are treatment-resistant to at least one AED.
• Willingness to not start a ketogenic diet during the Baseline or Treatment Period.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• Patient or parent(s)/caregiver(s) have daily commitments during the study duration that would interfere with attending all study visits.
• Has a history of nonfebrile seizures other than absence seizures.
• Has a history of febrile seizures after 3 years of age.
• Has a history consistent with juvenile absence epilepsy or juvenile myoclonic epilepsy.
• Currently taking felbamate.
• Currently taking phenytoin, fluvoxamine, carbamazepine, or St. John's Wort.
• 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).
• Currently on a ketogenic diet.
• 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.
• 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).
• History or presence of abnormal electrocardiograms (ECGs) that are clinically significant in the opinion of the investigator.
• Has a current or history of clinically significant intellectual disability or major psychiatric disease, including autism spectrum disorder, which would interfere with compliance.
• 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.
• Any history of attempted suicide.
• Previously received any investigational drug or device or investigational therapy within 30 days before Screening.

Sponsors & Collaborators

• Radius Pharmaceuticals, Inc.: lead

Study Sites (11)

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Pediatric Epilepsy and Neurology Specialists

Tampa, Florida, 33609, United States

Location

Clinical Integrative Research Center of Atlanta

Atlanta, Georgia, 30328, United States

Location

Clinical Research Center of Nevada

Henderson, Nevada, 89052, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Children's Specialty Group, Division of Child & Adolescent Neurology

Norfolk, Virginia, 23510, United States

Location

Research and Innovation/MultiCare Health System

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Conditions

Epilepsy, Absence

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Limitations and Caveats

This study was prematurely terminated by the Sponsor. Enrollment of Cohort 3 was discontinued.

Results Point of Contact

• Title: Tarek El Akkad, Head of Clinical Development
• Organization: Radius Pharmaceuticals, Inc.

telakkad@radiuspharm.com

6175514000

Study Officials

• Ahmed Elkashef, MD

  INSYS Therapeutics Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 8, 2017
• Study Start: December 29, 2017
• Primary Completion: May 15, 2019
• Study Completion: May 29, 2019
• Last Updated: July 21, 2023
• Results First Posted: July 21, 2023

Record last verified: 2023-07

Locations

US (11)