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

Sponsor
INSYS Therapeutics Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT02324673
Collaborator
(none)
61
Enrollment
10
Locations
3
Arms
12.9
Actual Duration (Months)
6.1
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Cannabidiol Oral Solution
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
61 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 13, 2015
Actual Primary Completion Date :
May 9, 2016
Actual Study Completion Date :
May 9, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Low Dose Cannabidiol Oral Solution [10 mg/kg/day]

Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10.

Drug: Cannabidiol Oral Solution
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Experimental: Mid Dose Cannabidiol Oral Solution [20 mg/kg/day]

Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10.

Drug: Cannabidiol Oral Solution
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Experimental: High Dose Cannabidiol Oral Solution [40 mg/kg/day]

High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.

Drug: Cannabidiol Oral Solution
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Outcome Measures

Primary Outcome Measures

  1. Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol [Day 1 at age-specific times]

    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.

  2. Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 10 at age-specific times]

    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.

  3. Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 1 at age-specific times]

    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.

  4. Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 10 at age-specific times]

    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.

  5. Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 1 at age-specific times]

    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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

  6. Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 10 at age-specific times]

    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.

  7. Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age [Day 1 at age-specific times]

    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.

  8. Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age [Day 1 at age-specific times]

    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.

  9. Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age [Day 1 at age-specific times]

    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.

  10. Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age [Day 1 at age-specific times]

    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.

  11. 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 [Day 1 at age-specific times]

    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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

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

    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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.

  13. 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 [Day 1 at age-specific times]

    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.

  14. 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 [Day 1 at age-specific times]

    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.

  15. 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 [Day 1 at age-specific times]

    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.

  16. Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1 [Day 1 at age-specific times]

    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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose. MRCmax was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).

  17. MRCmax on Day 10 [Day 10 at age-specific times]

    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. MRCmax was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).

  18. Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age [Day 1 at age-specific times]

    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. MRAUC(0-inf) was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).

  19. Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1 [Day 1 at age-specific times]

    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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose. MRAUC(0-12) was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).

  20. Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10 [Day 10 at age-specific times]

    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. MRAUC(0-12) was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).

  21. AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 [Day 10 at age-specific times]

    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.

  22. Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 [Day 10 at age-specific times]

    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.

  23. Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 10 at age-specific times]

    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.

  24. Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 10 at age-specific times]

    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.

  25. Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 10 at age-specific times]

    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.

  26. Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol [Day 10 at age-specific times]

    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.

  27. Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age [Day 1 and Day 10]

    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.

  28. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From the first dose of study drug up to Day 17]

    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.

  29. Clinical Global Impression of Improvement (CGI-I) Assessment [Day 11]

    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.

  30. Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment [Baseline and Day 11]

    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).

  31. Change From Baseline in Daily Seizure Activity [Baseline and Day 11]

    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.

  32. Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Day 11]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of California San Francisco Medical Center San Francisco California United States 94143
2 Miami Children's Hospital Miami Florida United States 33155
3 Child Neurology Center - NW F Pensacola Florida United States 32504
4 University of Chicago Medical Center Chicago Illinois United States 60637
5 Clinical Research Center of Nevada LLC Las Vegas Nevada United States 89104
6 Oregon Health Services University Portland Oregon United States 97239
7 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
8 Le Bonheur Children's Hospital Memphis Tennessee United States 38103
9 Texas Scottish Rite Hospital for Children Dallas Texas United States 79219
10 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)

None provided.

More Information

Publications

None provided.
Responsible Party:
INSYS Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT02324673
Other Study ID Numbers:
  • INS011-14-029
First Posted:
Dec 24, 2014
Last Update Posted:
Jun 23, 2017
Last Verified:
May 1, 2017
Keywords provided by INSYS Therapeutics Inc
Treatment-resistant seizures
Additional relevant MeSH terms:
Seizures
Epilepsy
Cannabidiol

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Period Title: Overall Study
STARTED 20 20 21
COMPLETED 20 20 21
NOT COMPLETED 0 0 0

Baseline Characteristics

Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day] Total
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10. Total of all reporting groups
Overall Participants 20 20 21 61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
7.5
(5.32)
7.7
(5.17)
7.8
(5.39)
7.6
(5.21)
Age, Customized (Count of Participants)
Infants = 1 to <2 years
5
25%
5
25%
5
23.8%
15
24.6%
Children = 2 to <12 years
9
45%
9
45%
10
47.6%
28
45.9%
Adolescents = 12 to ≤17 years
6
30%
6
30%
6
28.6%
18
29.5%
Sex: Female, Male (Count of Participants)
Female
10
50%
7
35%
11
52.4%
28
45.9%
Male
10
50%
13
65%
10
47.6%
33
54.1%
Region of Enrollment (Count of Participants)
United States
20
100%
20
100%
21
100%
61
100%

Outcome Measures

1. Primary Outcome
Title Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population (PK), all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for Cmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
59.03
(99.98)
110.5
(142.3)
256.9
(351.9)
7-OH Cannabidiol
28.71
(26.72)
61.89
(72.88)
140.9
(210.0)
2. Primary Outcome
Title Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for Cmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
119.6
(105.0)
220.0
(294.7)
426.8
(327.7)
7-OH Cannabidiol
79.38
(40.82)
136.6
(140.9)
286.1
(201.9)
3. Primary Outcome
Title Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for Cmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
11.72
(19.89)
10.77
(13.97)
13.25
(18.07)
7-OH Cannabidiol
5.737
(5.330)
5.990
(7.011)
7.286
(10.91)
4. Primary Outcome
Title Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for Cmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
23.79
(20.46)
21.16
(28.40)
21.40
(16.38)
7-OH Cannabidiol
15.82
(7.928)
13.10
(13.06)
14.39
(10.26)
5. Primary Outcome
Title Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.
Time Frame Day 1 at age-specific times

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for tmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
2.58
4.00
3.15
7-OH Cannabidiol
2.55
4.00
3.07
6. Primary Outcome
Title Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for tmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
2.99
2.00
3.00
7-OH Cannabidiol
2.08
2.03
2.03
7. Primary Outcome
Title Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age
Description 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

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for t1/2.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 15 15 16
Cannabidiol
31.31
(23.46)
33.48
(14.97)
21.58
(10.50)
7-OH Cannabidiol
19.71
(7.640)
31.84
(24.28)
14.77
(4.354)
8. Primary Outcome
Title Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age
Description 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

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for λz.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 15 15 16
Cannabidiol
0.02969
(0.01386)
0.02836
(0.02340)
0.03949
(0.01976)
7-OH Cannabidiol
0.04053
(0.01557)
0.03276
(0.01985)
0.05123
(0.01711)
9. Primary Outcome
Title Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age
Description 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

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for CL/F.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 10 8 12
Mean (Standard Deviation) [Liters (L)/h/kg]
29.78
(15.96)
21.10
(23.04)
31.29
(30.43)
10. Primary Outcome
Title Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age
Description 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

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for Vz/F.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 10 8 12
Mean (Standard Deviation) [L/kg]
1021
(609.1)
930.8
(1034)
982.6
(1119)
11. Primary Outcome
Title 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
Description 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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.
Time Frame Day 1 at age-specific times

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for AUC(0-12).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
173.9
(179.6)
507.1
(687.7)
914.5
(1155)
7-OH Cannabidiol
124.4
(80.18)
329.8
(402.9)
646.7
(886.3)
12. Primary Outcome
Title Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1
Description 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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.
Time Frame Day 1 at age-specific times

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for AUC(0-12)/D.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
34.60
(35.48)
49.23
(66.68)
47.13
(59.38)
7-OH Cannabidiol
24.88
(15.93)
31.77
(38.00)
33.39
(45.94)
13. Primary Outcome
Title 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
Description 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

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for AUC(0-last).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 15 15 16
Cannabidiol
250.0
(217.1)
692.5
(826.9)
1355
(1447)
7-OH Cannabidiol
212.2
(112.1)
544.9
(526.6)
1221
(1296)
14. Primary Outcome
Title 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
Description 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

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for AUC(0-inf).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 15 15 16
Cannabidiol
270.1
(256.7)
1140
(1118)
1584
(1709)
7-OH Cannabidiol
229.3
(122.3)
704.1
(627.8)
1354
(1428)
15. Primary Outcome
Title 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
Description 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

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for AUC(0-inf)/D.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 15 15 16
Cannabidiol
53.64
(50.04)
111.8
(111.2)
83.10
(87.93)
7-OH Cannabidiol
46.07
(24.63)
68.43
(62.34)
70.34
(73.66)
16. Primary Outcome
Title Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1
Description 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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose. MRCmax was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).
Time Frame Day 1 at age-specific times

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for MRCmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Mean (Standard Deviation) [ratio]
0.8935
(0.5543)
0.9328
(0.8332)
0.8081
(0.4849)
17. Primary Outcome
Title MRCmax on Day 10
Description 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. MRCmax was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).
Time Frame Day 10 at age-specific times

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for metabolite to parent ratio.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 17 21
Mean (Standard Deviation) [ratio]
0.7717
(0.3960)
0.8230
(0.3880)
0.7657
(0.4179)
18. Primary Outcome
Title Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age
Description 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. MRAUC(0-inf) was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).
Time Frame Day 1 at age-specific times

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for MRAUC(0-inf).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 10 8 12
Mean (Standard Deviation) [ratio]
0.9099
(0.5173)
0.9459
(0.4874)
0.9538
(0.4370)
19. Primary Outcome
Title Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1
Description 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, 8, 12, 16, 24, 36, 48 and 72 hours post-dose. MRAUC(0-12) was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).
Time Frame Day 1 at age-specific times

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for MRAUC(0-12).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 19 21
Mean (Standard Deviation) [ratio]
0.9309
(0.5229)
0.9793
(0.7147)
0.9085
(0.5075)
20. Primary Outcome
Title Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10
Description 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. MRAUC(0-12) was adjusted for molecular weight differences between cannabidiol (341.46) and 7-OH cannabidiol (330.46).
Time Frame Day 10 at age-specific times

Outcome Measure Data

Analysis Population Description
Participants ≥2 years from the PK Population who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for MRAUC(0-12).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 19 17 21
Mean (Standard Deviation) [ratio]
0.8795
(0.4084)
0.7866
(0.2361)
0.8700
(0.4304)
21. Primary Outcome
Title AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for AUC(0-12).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
581.6
(283.4)
1098
(976.4)
2708
(1789)
7-OH Cannabidiol
513.4
(269.0)
832.8
(675.2)
2165
(1405)
22. Primary Outcome
Title Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for AUC(0-12)/D.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
115.8
(55.32)
106.0
(94.64)
135.7
(89.17)
7-OH Cannabidiol
102.2
(53.01)
80.19
(63.53)
108.7
(70.76)
23. Primary Outcome
Title Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for Cmin.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
19.97
(8.798)
41.67
(25.41)
118.3
(75.82)
7-OH Cannabidiol
21.82
(13.23)
34.11
(23.99)
108.7
(70.87)
24. Primary Outcome
Title Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for Cavg.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
48.56
(23.58)
91.38
(80.92)
225.7
(149.3)
7-OH Cannabidiol
42.94
(22.54)
69.37
(56.09)
180.4
(117.1)
25. Primary Outcome
Title Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for RCmax.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
5.535
(5.551)
4.454
(4.466)
7.488
(11.93)
7-OH Cannabidiol
3.823
(2.730)
3.996
(3.544)
5.788
(6.028)
26. Primary Outcome
Title Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for RAUC(0-12).
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Cannabidiol
5.434
(3.625)
5.489
(4.633)
9.376
(15.11)
7-OH Cannabidiol
4.865
(2.748)
4.524
(3.338)
7.541
(7.187)
27. Primary Outcome
Title Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age
Description 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

Outcome Measure Data

Analysis Population Description
PK Population, all participants who received ≥1 dose of study drug and had ≥1 post-dose measured plasma concentration of cannabidiol and/or 7-OH cannabidiol with evaluable PK data available for analysis. The number of participants in each category is the number of participants with evaluable PK data available for time linearity index.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 15 15 16
Cannabidiol
3.211
(2.048)
2.628
(2.276)
4.201
(4.990)
7-OH Cannabidiol
2.500
(0.9365)
1.821
(1.162)
3.045
(2.260)
28. Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description 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

Outcome Measure Data

Analysis Population Description
Safety Analysis Population (SAF), all participants who received ≥1 dose of the investigational product.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
TEAE
13
65%
9
45%
17
81%
SAE
0
0%
1
5%
2
9.5%
29. Primary Outcome
Title Clinical Global Impression of Improvement (CGI-I) Assessment
Description 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

Outcome Measure Data

Analysis Population Description
Efficacy Analysis Population (EFF), all participants who received ≥1 dose of the investigational product and had ≥1 efficacy assessment for CGI-I post-dose.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Parents/Caregivers
2.1
(1.02)
2.4
(0.82)
2.3
(1.15)
Investigator
2.7
(0.92)
2.5
(0.94)
2.9
(0.91)
30. Primary Outcome
Title Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment
Description 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

Outcome Measure Data

Analysis Population Description
EFF, all participants who received ≥1 dose of the investigational product and had ≥1 efficacy assessment for CGI-S post-dose.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Parents/Caregivers
-1.7
(2.08)
-2.2
(2.04)
-1.8
(1.64)
Investigator
-1.1
(1.27)
-0.7
(1.15)
-0.7
(1.23)
31. Primary Outcome
Title Change From Baseline in Daily Seizure Activity
Description 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

Outcome Measure Data

Analysis Population Description
EFF, all participants who received ≥1 dose of the investigational product and had ≥1 efficacy assessment for number of seizures per day at Day 11.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 20 20 21
Number of Tonic Seizures
-0.8
(1.55)
-0.8
(1.59)
-2.9
(7.69)
Number of Atonic Seizures
-0.2
(0.98)
-0.1
(0.28)
0.0
(0.00)
32. Primary Outcome
Title Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description 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

Outcome Measure Data

Analysis Population Description
Participants from the Safety Analysis Population (SAF), all participants who received ≥1 dose of the investigational product, who completed the C-SSRS.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
Measure Participants 4 5 4
Suicide Ideation
0
0%
0
0%
0
0%
Suicide Behavior
0
0%
0
0%
0
0%

Adverse Events

Time Frame From the first dose of study drug to 7 days after the last dose of study drug (up to Day 17)
Adverse Event Reporting Description Participants who completed all study activities for this study had the option to participate in a rollover study. Participants who enrolled into the rollover study may not have had adverse event data collected after Day 11.
Arm/Group Title Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Arm/Group Description Low Dose [10 milligrams/kilogram/day (mg/kg/day)] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 5 mg/kg in the morning on Day 1 followed by total dose of 10 mg/kg/day (5 mg/kg in the morning and 5 mg/kg in the evening) on Days 4 to 10. Mid Dose [20 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 10 mg/kg in the morning on Day 1 followed by total dose of 20 mg/kg/day (10 mg/kg in the morning and 10 mg/kg in the evening) on Days 4 to 10. High Dose [40 mg/kg/day] oral solution containing pharmaceutical grade cannabidiol (nonplant-based). Starting dose of 20 mg/kg in the morning on Day 1 followed by total dose of 40 mg/kg/day (20 mg/kg in the morning and 20 mg/kg in the evening) on Days 4 to 10.
All Cause Mortality
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/20 (0%) 0/20 (0%) 0/21 (0%)
Serious Adverse Events
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/20 (0%) 1/20 (5%) 2/21 (9.5%)
Respiratory, thoracic and mediastinal disorders
Apnoea 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Skin and subcutaneous tissue disorders
Drug eruption 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Vascular disorders
Thrombophlebitis 0/20 (0%) 1/20 (5%) 0/21 (0%)
Other (Not Including Serious) Adverse Events
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] High Dose Cannabidiol Oral Solution [40 mg/kg/Day]
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 13/20 (65%) 9/20 (45%) 17/21 (81%)
Blood and lymphatic system disorders
Anaemia 2/20 (10%) 5/20 (25%) 4/21 (19%)
Cardiac disorders
Nodal rhythm 0/20 (0%) 1/20 (5%) 0/21 (0%)
Tachycardia 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Ear and labyrinth disorders
Ear pain 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Eye disorders
Eye pain 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Gastrointestinal disorders
Diarrhoea 1/20 (5%) 2/20 (10%) 7/21 (33.3%)
Flatulence 0/20 (0%) 2/20 (10%) 3/21 (14.3%)
Abdominal pain upper 2/20 (10%) 1/20 (5%) 0/21 (0%)
Vomiting 2/20 (10%) 1/20 (5%) 0/21 (0%)
Oral mucosal erythema 1/20 (5%) 0/20 (0%) 0/21 (0%)
Oral pain 1/20 (5%) 0/20 (0%) 0/21 (0%)
Dysphagia 0/20 (0%) 1/20 (5%) 0/21 (0%)
Constipation 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Gastrooesophageal reflux disease 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Nausea 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
General disorders
Catheter site pruritus 0/20 (0%) 2/20 (10%) 1/21 (4.8%)
Pyrexia 1/20 (5%) 0/20 (0%) 1/21 (4.8%)
Fatigue 1/20 (5%) 0/20 (0%) 0/21 (0%)
Thirst 1/20 (5%) 0/20 (0%) 0/21 (0%)
Injection site reaction 0/20 (0%) 1/20 (5%) 0/21 (0%)
Catheter site pain 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Infections and infestations
Lice infestation 1/20 (5%) 0/20 (0%) 0/21 (0%)
Upper respiratory tract infection 0/20 (0%) 1/20 (5%) 1/21 (4.8%)
Adenovirus infection 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Clostridium difficile infection 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Escherichia urinary tract infection 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Urinary tract infection 0/20 (0%) 1/20 (5%) 0/21 (0%)
Injury, poisoning and procedural complications
Skin abrasion 1/20 (5%) 0/20 (0%) 0/21 (0%)
Investigations
Weight increased 0/20 (0%) 1/20 (5%) 2/21 (9.5%)
Weight decreased 1/20 (5%) 0/20 (0%) 0/21 (0%)
Blood follicle stimulating hormone increased 0/20 (0%) 1/20 (5%) 0/21 (0%)
Blood follicle stimulating hormone decreased 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Urine analysis abnormal 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Alanine aminotransferase increase 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Metabolism and nutrition disorders
Decreased appetite 2/20 (10%) 0/20 (0%) 1/21 (4.8%)
Dehydration 0/20 (0%) 0/20 (0%) 2/21 (9.5%)
Metabolic acidosis 0/20 (0%) 0/20 (0%) 2/21 (9.5%)
Hyperphosphataemia 0/20 (0%) 1/20 (5%) 0/21 (0%)
Hypocalcaemia 0/20 (0%) 1/20 (5%) 0/21 (0%)
Hyperglycaemia 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Nervous system disorders
Somnolence 3/20 (15%) 3/20 (15%) 7/21 (33.3%)
Psychomotor hyperactivity 0/20 (0%) 2/20 (10%) 3/21 (14.3%)
Seizure 1/20 (5%) 1/20 (5%) 1/21 (4.8%)
Ataxia 0/20 (0%) 0/20 (0%) 2/21 (9.5%)
Hypersomnia 1/20 (5%) 0/20 (0%) 0/21 (0%)
Syncope 1/20 (5%) 0/20 (0%) 0/21 (0%)
Dizziness 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Headache 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Lethargy 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Sedation 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Tremor 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Psychiatric disorders
Insomnia 0/20 (0%) 1/20 (5%) 1/21 (4.8%)
Aggression 1/20 (5%) 0/20 (0%) 0/21 (0%)
Agitation 1/20 (5%) 0/20 (0%) 0/21 (0%)
Irritability 1/20 (5%) 0/20 (0%) 0/21 (0%)
Renal and urinary disorders
Proteinuria 0/20 (0%) 1/20 (5%) 0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 1/20 (5%) 1/20 (5%) 0/21 (0%)
Dyspnoea 1/20 (5%) 0/20 (0%) 0/21 (0%)
Rhinorrhoea 1/20 (5%) 0/20 (0%) 0/21 (0%)
Asthma 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Wheezing 0/20 (0%) 0/20 (0%) 1/21 (4.8%)
Skin and subcutaneous tissue disorders
Dermatitis contact 0/20 (0%) 2/20 (10%) 0/21 (0%)
Ecchymosis 0/20 (0%) 1/20 (5%) 1/21 (4.8%)
Dermatitis 1/20 (5%) 0/20 (0%) 0/21 (0%)
Rash macular 0/20 (0%) 1/20 (5%) 0/21 (0%)
Pruritus 0/20 (0%) 0/20 (0%) 1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Director, Clinical Development
Organization Insys Therapeutics, Inc.
Phone 480-500-3105
Email gdecastro@insysrx.com
Responsible Party:
INSYS Therapeutics Inc
ClinicalTrials.gov Identifier:
NCT02324673
Other Study ID Numbers:
  • INS011-14-029
First Posted:
Dec 24, 2014
Last Update Posted:
Jun 23, 2017
Last Verified:
May 1, 2017