Phase 2
N=61
Cannabidiol Oral Solution in Pediatric Participants With Treatment-resistant Seizure Disorders
Seizures
Bottom Line
View on ClinicalTrials.gov: NCT02324673 ↗Enrolled (actual)
61
Serious AEs
4.9%
Results posted
Jun 2017
Primary outcome: Primary: Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol — 59.03; 110.5; 256.9; 28.71 nanograms/milliliter (ng/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cannabidiol Oral Solution (Drug)
- Age
- Pediatric · 1+ yrs
- Sex
- All
- Sponsor
- INSYS Therapeutics Inc
- Primary completion
- May 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Plasma Concentration (Cmax) for Cannabidiol and Metabolite 7-hydroxy (7-OH) Cannabidiol |
59.03; 110.5; 256.9; 28.71; 61.89; 140.9 | — |
| PRIMARY Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol |
119.6; 220.0; 426.8; 79.38; 136.6; 286.1 | — |
| PRIMARY Dose Normalized Cmax (Cmax/D) for Cannabidiol and Metabolite 7-OH Cannabidiol |
11.72; 10.77; 13.25; 5.737; 5.990; 7.286 | — |
| PRIMARY Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol |
23.79; 21.16; 21.40; 15.82; 13.10; 14.39 | — |
| PRIMARY Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol |
2.99; 2.00; 3.00; 2.08; 2.03; 2.03 | — |
| PRIMARY Time to Cmax (Tmax) for Cannabidiol and Metabolite 7-OH Cannabidiol |
2.99; 2.00; 3.00; 2.08; 2.03; 2.03 | — |
| PRIMARY Half Life (t1/2) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age |
31.31; 33.48; 21.58; 19.71; 31.84; 14.77 | — |
| PRIMARY Elimination Rate (Lambda-z [λz]) for Cannabidiol and Metabolite 7-OH Cannabidiol for Participants ≥2 Years of Age |
0.02969; 0.02836; 0.03949; 0.04053; 0.03276; 0.05123 | — |
| PRIMARY Oral Clearance (CL/F) for Cannabidiol for Participants ≥2 Years of Age |
29.78; 21.10; 31.29 | — |
| PRIMARY Volume of Distribution (Vz/F) of Cannabidiol for Participants ≥2 Years of Age |
1021; 930.8; 982.6 | — |
| 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 |
173.9; 507.1; 914.5; 124.4; 329.8; 646.7 | — |
| PRIMARY Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 1 |
34.60; 49.23; 47.13; 24.88; 31.77; 33.39 | — |
| 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 |
250.0; 692.5; 1355; 212.2; 544.9; 1221 | — |
| 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 |
270.1; 1140; 1584; 229.3; 704.1; 1354 | — |
| 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 |
53.64; 111.8; 83.10; 46.07; 68.43; 70.34 | — |
| PRIMARY Metabolite (7-OH Cannabidiol) to Parent (Cannabidiol) Ratio for Cmax [MRCmax] on Day 1 |
0.8935; 0.9328; 0.8081 | — |
| PRIMARY MRCmax on Day 10 |
0.7717; 0.8230; 0.7657 | — |
| PRIMARY Metabolite to Parent Ratio for AUC(0-inf) [MRAUC(0-inf)] on Day 1 for Participants ≥2 Years of Age |
0.9099; 0.9459; 0.9538 | — |
| PRIMARY Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 1 |
0.9309; 0.9793; 0.9085 | — |
| PRIMARY Metabolite to Parent Ratio for AUC(0-12) [MRAUC(0-12)] on Day 10 |
0.8795; 0.7866; 0.8700 | — |
| PRIMARY AUC(0-12) for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 |
581.6; 1098; 2708; 513.4; 832.8; 2165 | — |
| PRIMARY Dose Normalized AUC(0-12) [AUC (0-12)/D] for Cannabidiol and Metabolite 7-OH Cannabidiol on Day 10 |
115.8; 106.0; 135.7; 102.2; 80.19; 108.7 | — |
| PRIMARY Minimum Plasma Concentration (Cmin) for Cannabidiol and Metabolite 7-OH Cannabidiol |
19.97; 41.67; 118.3; 21.82; 34.11; 108.7 | — |
| PRIMARY Average Plasma Concentration (Cavg) for Cannabidiol and Metabolite 7-OH Cannabidiol |
48.56; 91.38; 225.7; 42.94; 69.37; 180.4 | — |
| PRIMARY Accumulation Ratio for Cmax (RCmax) on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol |
5.535; 4.454; 7.488; 3.823; 3.996; 5.788 | — |
| PRIMARY Accumulation Ratio for AUC(0-12) [RAUC(0-12)] on Day 10 for Cannabidiol and Metabolite 7-OH Cannabidiol |
5.434; 5.489; 9.376; 4.865; 4.524; 7.541 | — |
| PRIMARY Time Linearity Index for Cannabidiol and Metabolite 7-OH Cannabidiol in Participants ≥2 Years of Age |
3.211; 2.628; 4.201; 2.500; 1.821; 3.045 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
13; 9; 17; 0; 1; 2 | — |
| PRIMARY Clinical Global Impression of Improvement (CGI-I) Assessment |
2.1; 2.4; 2.3; 2.7; 2.5; 2.9 | — |
| PRIMARY Change From Baseline in Clinical Global Impression of Severity (CGI-S) Assessment |
-1.7; -2.2; -1.8; -1.1; -0.7; -0.7 | — |
| PRIMARY Change From Baseline in Daily Seizure Activity |
-0.8; -0.8; -2.9; -0.2; -0.1; 0.0 | — |
| PRIMARY Number of Participants With Suicide Related Thoughts and Behaviors Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) |
0; 0; 0; 0; 0; 0 | — |
Summary
This is a Phase 1/2, open-label trial designed to assess the pharmacokinetics, safety, tolerability, and preliminary efficacy of 3 multiple ascending doses of Cannabidiol Oral Solution in a sequential fashion.
Participants will be pediatric (aged 1-17, inclusive), experiencing treatment-resistant seizures, and satisfy all inclusion/exclusion criteria.
Eligibility Criteria
Inclusion Criteria
- Meets protocol-specified criteria for qualification and contraception, including treatment-resistant seizure disorder
- Is able to speak and understand the language in which the study is being conducted, is able to understand the procedures and study requirements and has voluntarily signed and dated an informed consent form approved by the Institutional Review Board before the conduct of any study procedure
- In the opinion of the Investigator, the participants and parent(s)/caregiver(s) are willing and able to comply with the study procedures and visit schedules, including venipuncture, inpatient stay at the study center, dosing at the study center twice a day as needed while an outpatient), and the Follow-up Visits (if applicable)
Exclusion Criteria
- Participant or parent(s)/caregiver(s) have daily commitments during the study duration that would interfere with attending all study visits
- History or current use of dietary supplements, drugs or over-the counter medications outside protocol-specified parameters
- Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:
- the safety or well-being of the participant or study staff
- the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding)
- the analysis of results
Data sourced from ClinicalTrials.gov (NCT02324673). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.