Clinical trial NCT02324673: Cannabidiol Oral Solution in Pediatric Participants With Treatment-resistant Seizure Disorders
Official title: A Phase 1/2 Study to Assess the Pharmacokinetics and Safety of Multiple Doses of Pharmaceutical Cannabidiol Oral Solution in Pediatric Participants With Treatment-Resistant Seizure Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Seizures
Keywords: Treatment-resistant seizures
Lead sponsor: INSYS Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2014-12-24
Enrollment: 61
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol
timeFrame: Day 1 at age-specific times
measure: Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 10 at age-specific times
measure: Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 1 at age-specific times
measure: Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 10 at age-specific times
measure: Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 1 at age-specific times
measure: Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 10 at age-specific times
measure: Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age
timeFrame: Day 1 at age-specific times
measure: Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age
timeFrame: Day 1 at age-specific times
measure: Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age
timeFrame: Day 1 at age-specific times
measure: Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age
timeFrame: Day 1 at age-specific times
measure: 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
timeFrame: Day 1 at age-specific times
measure: Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1
timeFrame: Day 1 at age-specific times
measure: 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
timeFrame: Day 1 at age-specific times
measure: 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
timeFrame: Day 1 at age-specific times
measure: 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
timeFrame: Day 1 at age-specific times
measure: Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1
timeFrame: Day 1 at age-specific times
measure: MRCmax on Day 10
timeFrame: Day 10 at age-specific times
measure: Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age
timeFrame: Day 1 at age-specific times
measure: Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1
timeFrame: Day 1 at age-specific times
measure: Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10
timeFrame: Day 10 at age-specific times
measure: AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10
timeFrame: Day 10 at age-specific times
measure: Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10
timeFrame: Day 10 at age-specific times
measure: Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 10 at age-specific times
measure: Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 10 at age-specific times
measure: Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 10 at age-specific times
measure: Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol
timeFrame: Day 10 at age-specific times
measure: Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age
timeFrame: Day 1 and Day 10
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug up to Day 17
measure: Clinical Global Impression of Improvement (CGI-I) Assessment
timeFrame: Day 11
measure: Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment
timeFrame: Baseline and Day 11
measure: Change From Baseline in Daily Seizure Activity
timeFrame: Baseline and Day 11
measure: Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Day 11
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Child Neurology Center - NW F
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada LLC
state: Nevada
city: Portland
country: United States
facility: Oregon Health Services University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: Texas Scottish Rite Hospital for Children
state: Texas
city: Tacoma
country: United States
facility: Mary Bridge Children's Hospital
state: Washington
Study officials:
affiliation: INSYS Therapeutics Inc
name: Neha Parikh
role: STUDY_DIRECTOR
References:
citation: Wheless JW, Dlugos D, Miller I, Oh DA, Parikh N, Phillips S, Renfroe JB, Roberts CM, Saeed I, Sparagana SP, Yu J, Cilio MR; INS011-14-029 Study Investigators. Pharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy. CNS Drugs. 2019 Jun;33(6):593-604. doi: 10.1007/s40263-019-00624-4.