Cannabidiol Oral Solution in Pediatric Participants With Treatment-resistant Seizure Disorders

INSYS Therapeutics Inc61 enrolled

Overview

This is a Phase 1/2, open-label trial designed to assess the pharmacokinetics, safety, tolerability, and preliminary efficacy of 3 multiple ascending doses of Cannabidiol Oral Solution in a sequential fashion. Participants will be pediatric (aged 1-17, inclusive), experiencing treatment-resistant seizures, and satisfy all inclusion/exclusion criteria.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Seizures

Interventions

Cannabidiol Oral SolutionDRUG

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

Eligibility

Sex: ALLMin age: 1 YearMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Meets protocol-specified criteria for qualification and contraception, including treatment-resistant seizure disorder * Is able to speak and understand the language in which the study is being conducted, is able to understand the procedures and study requirements and has voluntarily signed and dated an informed consent form approved by the Institutional Review Board before the conduct of any study procedure * In the opinion of the Investigator, the participants and parent(s)/caregiver(s) are willing and able to comply with the study procedures and visit schedules, including venipuncture, inpatient stay at the study center, dosing at the study center twice a day as needed while an outpatient), and the Follow-up Visits (if applicable) Exclusion Criteria: * Participant or parent(s)/caregiver(s) have daily commitments during the study duration that would interfere with attending all study visits * 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

Locations (10)

University of California San Francisco Medical Center

San Francisco, California, United States

Miami Children's Hospital

Miami, Florida, United States

Child Neurology Center - NW F

Pensacola, Florida, United States

Outcomes

Primary Outcomes

Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol

Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 1 at 2, 4, 8, 12 hours post-dose; Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

Time frame: Day 1 at age-specific times

Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol

Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.

Time frame: Day 10 at age-specific times

Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol

Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2: Day 1 at 2, 4, 8, 12 hours post-dose; Participants ages 2 to \<6: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17: Day 1 pre-dose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

Time frame: Day 1 at age-specific times

Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol

Time frame: Day 10 at age-specific times

Data from ClinicalTrials.gov

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University of Chicago Medical Center

Chicago, Illinois, United States

Clinical Research Center of Nevada LLC

Las Vegas, Nevada, United States

Oregon Health Services University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Texas Scottish Rite Hospital for Children

Dallas, Texas, United States

Mary Bridge Children's Hospital

Tacoma, Washington, United States

Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol

Time frame: Day 1 at age-specific times

Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol

Time frame: Day 10 at age-specific times

Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age

Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis.

Time frame: Day 1 at age-specific times

Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age

Time frame: Day 1 at age-specific times

Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age

Time frame: Day 1 at age-specific times

Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age

Time frame: Day 1 at age-specific times

Area Under the Plasma-Concentration Time Curve From 0 to 12 Hours Post-dose [AUC(0-12)] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1

Time frame: Day 1 at age-specific times

Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1

Time frame: Day 1 at age-specific times

AUC From Time 0 to the Last Quantifiable Concentration [AUC(0-last)] on Day 1 for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 for Participants ≥2 Years of Age

Time frame: Day 1 at age-specific times

AUC From Time 0 to Infinity [AUC(0-inf)] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 for Participants ≥2 Years of Age

Time frame: Day 1 at age-specific times

Dose Normalized AUC(0-inf) [AUC(0-inf)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 for Participants ≥2 Years of Age

Time frame: Day 1 at age-specific times

Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1

Time frame: Day 1 at age-specific times

MRCmax on Day 10

Time frame: Day 10 at age-specific times

Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age

Time frame: Day 1 at age-specific times

Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1

Time frame: Day 1 at age-specific times

Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10

Time frame: Day 10 at age-specific times

AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10

Time frame: Day 10 at age-specific times

Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10

Time frame: Day 10 at age-specific times

Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol

Time frame: Day 10 at age-specific times

Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol

Time frame: Day 10 at age-specific times

Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol

RCmax is the ratio of Cmax at Day 10 compared to Cmax at Day 1. Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.

Time frame: Day 10 at age-specific times

Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol

RAUC(0-12) is the ratio of AUC(0-12) at Day 10 compared to AUC(0-12) at Day 1. Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.

Time frame: Day 10 at age-specific times

Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age

Time linearity index is calculated as the ratio of AUC(0-12) on Day 10/AUC\[0-inf\] on Day 1. Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis.

Time frame: Day 1 and Day 10

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product. It does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event not present prior to the initiation of the treatment or any event already present that worsens. Any laboratory (clinical chemistry, hematology, urinalysis), 12-lead electrocardiograms, vital signs (temperature, blood pressure, pulse rate, respiratory rate) and physical examination findings deemed by the investigator to be clinically significant were captured as AEs. 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.

Time frame: From the first dose of study drug up to Day 17

Clinical Global Impression of Improvement (CGI-I) Assessment

The CGI-I was completed by the parents/caregivers and the investigator and was used to assess participants global status of their condition on Day 11 using a 7-point scale, where 1=very much improved and 7=very much worse since the initiation of treatment.

Time frame: Day 11

Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment

The CGI-S was completed by the parents/caregivers and the Investigator and was used to rate participant's mental illness status at Baseline (Screening) and Day 11 using a 7-point scale, where 1=normal, not mentally ill, and 7=among the most extremely mentally ill participants. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. The change in CGI-S score at Day 11 relative to Baseline is reported. A negative change from Baseline indicates improvement (decreased severity in illness).

Time frame: Baseline and Day 11

Change From Baseline in Daily Seizure Activity

The specific number of tonic and atonic seizures per study day were recorded in a diary. The change in number of seizures at Day 11 relative to Baseline is reported. A negative change from Baseline indicates an improvement based on Daily Seizure Activity.

Time frame: Baseline and Day 11

Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

The C-SSRS captured the occurrence, severity, and frequency of suicide related thoughts and behaviors at Day 11. The C-SSRS was only used for participants ≥ 7 years of age. The number of participants with results of "Yes" for Suicidal Ideation (Wish to be Dead and Non-Specific Active Suicidal Thoughts) and Suicidal Behavior (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior, and Suicidal Behavior) are reported.

Time frame: Day 11