Seizures
Conditions
Keywords
Treatment-resistant seizures
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.
Interventions
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Sponsors
INSYS Therapeutics Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 20 |
| 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. | 20 |
| 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. | 21 |
| Total | 61 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|
| Age, Continuous | 7.5 years STANDARD_DEVIATION 5.32 | 7.7 years STANDARD_DEVIATION 5.17 | 7.8 years STANDARD_DEVIATION 5.39 | 7.6 years STANDARD_DEVIATION 5.21 |
| Age, Customized Adolescents = 12 to ≤17 years | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Age, Customized Children = 2 to <12 years | 9 Participants | 9 Participants | 10 Participants | 28 Participants |
| Age, Customized Infants = 1 to <2 years | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Region of Enrollment United States | 20 Participants | 20 Participants | 21 Participants | 61 Participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 11 Participants | 28 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 10 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 21 |
| other Total, other adverse events | 13 / 20 | 9 / 20 | 17 / 21 |
| serious Total, serious adverse events | 0 / 20 | 1 / 20 | 2 / 21 |
Outcome results
Primary
Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol
RAUC(0-12) is the ratio of AUC(0-12) at Day 10 compared to AUC(0-12) at Day 1. Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.
Time frame: Day 10 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 5.434 ratio | Standard Deviation 3.625 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 4.865 ratio | Standard Deviation 2.748 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 5.489 ratio | Standard Deviation 4.633 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 4.524 ratio | Standard Deviation 3.338 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 9.376 ratio | Standard Deviation 15.11 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 7.541 ratio | Standard Deviation 7.187 |
Primary
Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol
RCmax is the ratio of Cmax at Day 10 compared to Cmax at Day 1. Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.
Time frame: Day 10 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 5.535 ratio | Standard Deviation 5.551 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 3.823 ratio | Standard Deviation 2.73 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 4.454 ratio | Standard Deviation 4.466 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 3.996 ratio | Standard Deviation 3.544 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 7.488 ratio | Standard Deviation 11.93 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 5.788 ratio | Standard Deviation 6.028 |
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | Cannabidiol | 173.9 ng*h/mL | Standard Deviation 179.6 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | 7-OH Cannabidiol | 124.4 ng*h/mL | Standard Deviation 80.18 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | Cannabidiol | 507.1 ng*h/mL | Standard Deviation 687.7 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | 7-OH Cannabidiol | 329.8 ng*h/mL | Standard Deviation 402.9 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | Cannabidiol | 914.5 ng*h/mL | Standard Deviation 1155 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | 7-OH Cannabidiol | 646.7 ng*h/mL | Standard Deviation 886.3 |
Primary
AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | Cannabidiol | 581.6 ng*h/mL | Standard Deviation 283.4 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | 7-OH Cannabidiol | 513.4 ng*h/mL | Standard Deviation 269 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | Cannabidiol | 1098 ng*h/mL | Standard Deviation 976.4 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | 7-OH Cannabidiol | 832.8 ng*h/mL | Standard Deviation 675.2 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | Cannabidiol | 2708 ng*h/mL | Standard Deviation 1789 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | 7-OH Cannabidiol | 2165 ng*h/mL | Standard Deviation 1405 |
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | Cannabidiol | 270.1 ng*h/mL | Standard Deviation 256.7 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | 7-OH Cannabidiol | 229.3 ng*h/mL | Standard Deviation 122.3 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | Cannabidiol | 1140 ng*h/mL | Standard Deviation 1118 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | 7-OH Cannabidiol | 704.1 ng*h/mL | Standard Deviation 627.8 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | Cannabidiol | 1584 ng*h/mL | Standard Deviation 1709 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | 7-OH Cannabidiol | 1354 ng*h/mL | Standard Deviation 1428 |
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | Cannabidiol | 250.0 ng*h/mL | Standard Deviation 217.1 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | 7-OH Cannabidiol | 212.2 ng*h/mL | Standard Deviation 112.1 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | Cannabidiol | 692.5 ng*h/mL | Standard Deviation 826.9 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | 7-OH Cannabidiol | 544.9 ng*h/mL | Standard Deviation 526.6 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | Cannabidiol | 1355 ng*h/mL | Standard Deviation 1447 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | 7-OH Cannabidiol | 1221 ng*h/mL | Standard Deviation 1296 |
Primary
Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.
Time frame: Day 10 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 48.56 ng/mL | Standard Deviation 23.58 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 42.94 ng/mL | Standard Deviation 22.54 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 91.38 ng/mL | Standard Deviation 80.92 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 69.37 ng/mL | Standard Deviation 56.09 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 225.7 ng/mL | Standard Deviation 149.3 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 180.4 ng/mL | Standard Deviation 117.1 |
Primary
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment
The CGI-S was completed by the parents/caregivers and the Investigator and was used to rate participant's mental illness status at Baseline (Screening) and Day 11 using a 7-point scale, where 1=normal, not mentally ill, and 7=among the most extremely mentally ill participants. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. The change in CGI-S score at Day 11 relative to Baseline is reported. A negative change from Baseline indicates improvement (decreased severity in illness).
Time frame: Baseline and Day 11
Population: EFF, all participants who received ≥1 dose of the investigational product and had ≥1 efficacy assessment for CGI-S post-dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment | Parents/Caregivers | -1.7 scores on a scale | Standard Deviation 2.08 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment | Investigator | -1.1 scores on a scale | Standard Deviation 1.27 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment | Parents/Caregivers | -2.2 scores on a scale | Standard Deviation 2.04 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment | Investigator | -0.7 scores on a scale | Standard Deviation 1.15 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment | Parents/Caregivers | -1.8 scores on a scale | Standard Deviation 1.64 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment | Investigator | -0.7 scores on a scale | Standard Deviation 1.23 |
Primary
Change From Baseline in Daily Seizure Activity
The specific number of tonic and atonic seizures per study day were recorded in a diary. The change in number of seizures at Day 11 relative to Baseline is reported. A negative change from Baseline indicates an improvement based on Daily Seizure Activity.
Time frame: Baseline and Day 11
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Change From Baseline in Daily Seizure Activity | Number of Tonic Seizures | -0.8 number of seizures per day | Standard Deviation 1.55 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Change From Baseline in Daily Seizure Activity | Number of Atonic Seizures | -0.2 number of seizures per day | Standard Deviation 0.98 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Change From Baseline in Daily Seizure Activity | Number of Atonic Seizures | -0.1 number of seizures per day | Standard Deviation 0.28 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Change From Baseline in Daily Seizure Activity | Number of Tonic Seizures | -0.8 number of seizures per day | Standard Deviation 1.59 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Change From Baseline in Daily Seizure Activity | Number of Tonic Seizures | -2.9 number of seizures per day | Standard Deviation 7.69 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Change From Baseline in Daily Seizure Activity | Number of Atonic Seizures | 0.0 number of seizures per day | Standard Deviation 0 |
Primary
Clinical Global Impression of Improvement (CGI-I) Assessment
The CGI-I was completed by the parents/caregivers and the investigator and was used to assess participants global status of their condition on Day 11 using a 7-point scale, where 1=very much improved and 7=very much worse since the initiation of treatment.
Time frame: Day 11
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Clinical Global Impression of Improvement (CGI-I) Assessment | Parents/Caregivers | 2.1 scores on a scale | Standard Deviation 1.02 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Clinical Global Impression of Improvement (CGI-I) Assessment | Investigator | 2.7 scores on a scale | Standard Deviation 0.92 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Clinical Global Impression of Improvement (CGI-I) Assessment | Parents/Caregivers | 2.4 scores on a scale | Standard Deviation 0.82 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Clinical Global Impression of Improvement (CGI-I) Assessment | Investigator | 2.5 scores on a scale | Standard Deviation 0.94 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Clinical Global Impression of Improvement (CGI-I) Assessment | Parents/Caregivers | 2.3 scores on a scale | Standard Deviation 1.15 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Clinical Global Impression of Improvement (CGI-I) Assessment | Investigator | 2.9 scores on a scale | Standard Deviation 0.91 |
Primary
Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 23.79 ng/mL/(mg/kg) | Standard Deviation 20.46 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 15.82 ng/mL/(mg/kg) | Standard Deviation 7.928 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 21.16 ng/mL/(mg/kg) | Standard Deviation 28.4 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 13.10 ng/mL/(mg/kg) | Standard Deviation 13.06 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 21.40 ng/mL/(mg/kg) | Standard Deviation 16.38 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 14.39 ng/mL/(mg/kg) | Standard Deviation 10.26 |
Primary
Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.
Time frame: Day 10 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 119.6 ng/mL | Standard Deviation 105 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 79.38 ng/mL | Standard Deviation 40.82 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 220.0 ng/mL | Standard Deviation 294.7 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 136.6 ng/mL | Standard Deviation 140.9 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 426.8 ng/mL | Standard Deviation 327.7 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 286.1 ng/mL | Standard Deviation 201.9 |
Primary
Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on 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 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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 | Cannabidiol | 34.60 ng*h/mL | Standard Deviation 35.48 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 | 7-OH Cannabidiol | 24.88 ng*h/mL | Standard Deviation 15.93 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 | Cannabidiol | 49.23 ng*h/mL | Standard Deviation 66.68 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 | 7-OH Cannabidiol | 31.77 ng*h/mL | Standard Deviation 38 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 | Cannabidiol | 47.13 ng*h/mL | Standard Deviation 59.38 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 | 7-OH Cannabidiol | 33.39 ng*h/mL | Standard Deviation 45.94 |
Primary
Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | Cannabidiol | 115.8 ng*h/mL/(mg/kg) | Standard Deviation 55.32 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | 7-OH Cannabidiol | 102.2 ng*h/mL/(mg/kg) | Standard Deviation 53.01 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | Cannabidiol | 106.0 ng*h/mL/(mg/kg) | Standard Deviation 94.64 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | 7-OH Cannabidiol | 80.19 ng*h/mL/(mg/kg) | Standard Deviation 63.53 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | Cannabidiol | 135.7 ng*h/mL/(mg/kg) | Standard Deviation 89.17 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 | 7-OH Cannabidiol | 108.7 ng*h/mL/(mg/kg) | Standard Deviation 70.76 |
Primary
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | Cannabidiol | 53.64 ng*h/mL/(mg/kg) | Standard Deviation 50.04 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | 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 | 7-OH Cannabidiol | 46.07 ng*h/mL/(mg/kg) | Standard Deviation 24.63 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | Cannabidiol | 111.8 ng*h/mL/(mg/kg) | Standard Deviation 111.2 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | 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 | 7-OH Cannabidiol | 68.43 ng*h/mL/(mg/kg) | Standard Deviation 62.34 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | Cannabidiol | 83.10 ng*h/mL/(mg/kg) | Standard Deviation 87.93 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | 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 | 7-OH Cannabidiol | 70.34 ng*h/mL/(mg/kg) | Standard Deviation 73.66 |
Primary
Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2: Day 1 at 2, 4, 8, 12 hours post-dose; Participants ages 2 to \<6: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17: Day 1 pre-dose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.
Time frame: Day 1 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 11.72 ng/mL/(mg/kg) | Standard Deviation 19.89 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 5.737 ng/mL/(mg/kg) | Standard Deviation 5.33 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 10.77 ng/mL/(mg/kg) | Standard Deviation 13.97 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 5.990 ng/mL/(mg/kg) | Standard Deviation 7.011 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 13.25 ng/mL/(mg/kg) | Standard Deviation 18.07 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 7.286 ng/mL/(mg/kg) | Standard Deviation 10.91 |
Primary
Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis.
Time frame: Day 1 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | Cannabidiol | 0.02969 1/h | Standard Deviation 0.01386 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | 7-OH Cannabidiol | 0.04053 1/h | Standard Deviation 0.01557 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | Cannabidiol | 0.02836 1/h | Standard Deviation 0.0234 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | 7-OH Cannabidiol | 0.03276 1/h | Standard Deviation 0.01985 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | Cannabidiol | 0.03949 1/h | Standard Deviation 0.01976 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | 7-OH Cannabidiol | 0.05123 1/h | Standard Deviation 0.01711 |
Primary
Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis.
Time frame: Day 1 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | Cannabidiol | 31.31 h | Standard Deviation 23.46 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | 7-OH Cannabidiol | 19.71 h | Standard Deviation 7.64 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | Cannabidiol | 33.48 h | Standard Deviation 14.97 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | 7-OH Cannabidiol | 31.84 h | Standard Deviation 24.28 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | Cannabidiol | 21.58 h | Standard Deviation 10.5 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age | 7-OH Cannabidiol | 14.77 h | Standard Deviation 4.354 |
Primary
Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 1 at 2, 4, 8, 12 hours post-dose; Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours post-dose.
Time frame: Day 1 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol | Cannabidiol | 59.03 nanograms/milliliter (ng/mL) | Standard Deviation 99.98 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol | 7-OH Cannabidiol | 28.71 nanograms/milliliter (ng/mL) | Standard Deviation 26.72 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol | Cannabidiol | 110.5 nanograms/milliliter (ng/mL) | Standard Deviation 142.3 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol | 7-OH Cannabidiol | 61.89 nanograms/milliliter (ng/mL) | Standard Deviation 72.88 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol | Cannabidiol | 256.9 nanograms/milliliter (ng/mL) | Standard Deviation 351.9 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol | 7-OH Cannabidiol | 140.9 nanograms/milliliter (ng/mL) | Standard Deviation 210 |
Primary
Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on 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 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1 | 0.8935 ratio | Standard Deviation 0.5543 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1 | 0.9328 ratio | Standard Deviation 0.8332 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1 | 0.8081 ratio | Standard Deviation 0.4849 |
Primary
Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on 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 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1 | 0.9309 ratio | Standard Deviation 0.5229 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1 | 0.9793 ratio | Standard Deviation 0.7147 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1 | 0.9085 ratio | Standard Deviation 0.5075 |
Primary
Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10 | 0.8795 ratio | Standard Deviation 0.4084 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10 | 0.7866 ratio | Standard Deviation 0.2361 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10 | 0.8700 ratio | Standard Deviation 0.4304 |
Primary
Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis. 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age | 0.9099 ratio | Standard Deviation 0.5173 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age | 0.9459 ratio | Standard Deviation 0.4874 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age | 0.9538 ratio | Standard Deviation 0.437 |
Primary
Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.
Time frame: Day 10 at age-specific times
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 19.97 ng/mL | Standard Deviation 8.798 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 21.82 ng/mL | Standard Deviation 13.23 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 41.67 ng/mL | Standard Deviation 25.41 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 34.11 ng/mL | Standard Deviation 23.99 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 118.3 ng/mL | Standard Deviation 75.82 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 108.7 ng/mL | Standard Deviation 70.87 |
Primary
MRCmax on Day 10
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | MRCmax on Day 10 | 0.7717 ratio | Standard Deviation 0.396 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | MRCmax on Day 10 | 0.8230 ratio | Standard Deviation 0.388 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | MRCmax on Day 10 | 0.7657 ratio | Standard Deviation 0.4179 |
Primary
Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS captured the occurrence, severity, and frequency of suicide related thoughts and behaviors at Day 11. The C-SSRS was only used for participants ≥ 7 years of age. The number of participants with results of Yes for Suicidal Ideation (Wish to be Dead and Non-Specific Active Suicidal Thoughts) and Suicidal Behavior (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior, and Suicidal Behavior) are reported.
Time frame: Day 11
Population: Participants from the Safety Analysis Population (SAF), all participants who received ≥1 dose of the investigational product, who completed the C-SSRS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicide Ideation | 0 Participants |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicide Behavior | 0 Participants |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicide Ideation | 0 Participants |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicide Behavior | 0 Participants |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicide Ideation | 0 Participants |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicide Behavior | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product. It does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event not present prior to the initiation of the treatment or any event already present that worsens. Any laboratory (clinical chemistry, hematology, urinalysis), 12-lead electrocardiograms, vital signs (temperature, blood pressure, pulse rate, respiratory rate) and physical examination findings deemed by the investigator to be clinically significant were captured as AEs. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires the participant be at a risk of death at the time of the event, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, or other serious event that requires medical or surgical intervention.
Time frame: From the first dose of study drug up to Day 17
Population: Safety Analysis Population (SAF), all participants who received ≥1 dose of the investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 13 Participants |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 0 Participants |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 9 Participants |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 1 Participants |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAE | 17 Participants |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 2 Participants |
Primary
Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis.
Time frame: Day 1 at age-specific times
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age | 29.78 Liters (L)/h/kg | Standard Deviation 15.96 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age | 21.10 Liters (L)/h/kg | Standard Deviation 23.04 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age | 31.29 Liters (L)/h/kg | Standard Deviation 30.43 |
Primary
Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age
Time linearity index is calculated as the ratio of AUC(0-12) on Day 10/AUC\[0-inf\] on Day 1. Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis.
Time frame: Day 1 and Day 10
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age | Cannabidiol | 3.211 ratio | Standard Deviation 2.048 |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age | 7-OH Cannabidiol | 2.500 ratio | Standard Deviation 0.9365 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age | Cannabidiol | 2.628 ratio | Standard Deviation 2.276 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age | 7-OH Cannabidiol | 1.821 ratio | Standard Deviation 1.162 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age | Cannabidiol | 4.201 ratio | Standard Deviation 4.99 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age | 7-OH Cannabidiol | 3.045 ratio | Standard Deviation 2.26 |
Primary
Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 10 pre-dose and at 2, 4, 8 and 12 hours post-dose; Participants ages 2 to \<6 years: Day 10 pre-dose and at 1, 2, 3, 4, 8, 12 and 24 hours post-dose; Participants ages 6 to ≤17 years: Day 10 pre-dose and at 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose.
Time frame: Day 10 at age-specific times
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 2.99 h |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 2.08 h |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 2.00 h |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 2.03 h |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 3.00 h |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 2.03 h |
Primary
Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 1 to \<2 years: Day 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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 2.58 hours (h) |
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 2.55 hours (h) |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 4.00 hours (h) |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 4.00 hours (h) |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | Cannabidiol | 3.15 hours (h) |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol | 7-OH Cannabidiol | 3.07 hours (h) |
Primary
Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age
Serial blood sample collection times for pharmacokinetic (PK) analysis were based on the participant's age as follows: Participants ages 2 to \<6 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24 and 48 hours post-dose; Participants ages 6 to ≤17 years: Day 1 pre-dose and at 1, 2, 3, 4, 8, 12, 16, 24, 36, 48 and 72 hours post-dose; Participants ages 1 to \<2 years were not included in this analysis.
Time frame: Day 1 at age-specific times
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Cannabidiol Oral Solution [10 mg/kg/Day] | Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age | 1021 L/kg | Standard Deviation 609.1 |
| Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day] | Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age | 930.8 L/kg | Standard Deviation 1034 |
| High Dose Cannabidiol Oral Solution [40 mg/kg/Day] | Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age | 982.6 L/kg | Standard Deviation 1119 |