NCT02324673

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

Completed Phase 1, PHASE2 Results posted Last updated 23 June 2017

What this trial tests

Phase 1, PHASE2 trial testing Cannabidiol Oral Solution in Seizures in 61 participants. Completed in 9 May 2016.

Timeline

13 April 2015

Primary endpoint
9 May 2016

9 May 2016

Quick facts

Lead sponsor	INSYS Therapeutics Inc
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	61
Start date	13 April 2015
Primary completion	9 May 2016
Estimated completion	9 May 2016
Sites	10 locations across United States

Drugs / interventions tested

• Cannabidiol Oral Solution — full drug profile →

Conditions studied

• Seizures — all drugs for Seizures →

Sponsor

INSYS Therapeutics Inc — full company profile →

Who can join

Adults 1 to 17, any sex, with Seizures. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	59.03	± 99.98
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	110.5	± 142.3
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	256.9	± 351.9

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	28.71	± 26.72
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	61.89	± 72.88
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	140.9	± 210.0

Cmax for Cannabidiol and Metabolite 7-OH Cannabidiol Primary · 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.

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	119.6	± 105.0
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	220.0	± 294.7
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	426.8	± 327.7

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	79.38	± 40.82
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	136.6	± 140.9
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	286.1	± 201.9

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

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	11.72	± 19.89
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	10.77	± 13.97
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	13.25	± 18.07

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	5.737	± 5.330
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	5.990	± 7.011
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	7.286	± 10.91

Cmax/D for Cannabidiol and Metabolite 7-OH Cannabidiol Primary · 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.

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	23.79	± 20.46
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	21.16	± 28.40
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	21.40	± 16.38

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	15.82	± 7.928
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	13.10	± 13.06
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	14.39	± 10.26

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

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	2.58	1.02 – 8.00
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	4.00	1.00 – 8.08
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	3.15	1.00 – 24.02

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	2.55	1.00 – 6.08
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	4.00	1.00 – 11.95
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	3.07	1.00 – 12.05

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

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	2.99	1.00 – 4.25
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	2.00	0.00 – 6.00
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	3.00	0.00 – 6.02

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	2.08	1.00 – 4.08
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	2.03	1.00 – 6.05
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	2.03	0.00 – 5.90

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

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	31.31	± 23.46
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	33.48	± 14.97
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	21.58	± 10.50

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	19.71	± 7.640
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	31.84	± 24.28
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	14.77	± 4.354

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

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	0.02969	± 0.01386
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	0.02836	± 0.02340
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	0.03949	± 0.01976

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	0.04053	± 0.01557
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	0.03276	± 0.01985
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	0.05123	± 0.01711

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

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	29.78	± 15.96
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	21.10	± 23.04
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	31.29	± 30.43

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

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	1021	± 609.1
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	930.8	± 1034
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	982.6	± 1119

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 Primary · 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.

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	173.9	± 179.6
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	507.1	± 687.7
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	914.5	± 1155

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	124.4	± 80.18
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	329.8	± 402.9
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	646.7	± 886.3

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

Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	34.60	± 35.48
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	49.23	± 66.68
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	47.13	± 59.38

7-OH Cannabidiol

Group	Value	95% CI
Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]	24.88	± 15.93
Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]	31.77	± 38.00
High Dose Cannabidiol Oral Solution [40 mg/kg/Day]	33.39	± 45.94

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug to 7 days after the last dose of study drug (up to Day 17). Reporting threshold: 4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Low Dose Cannabidiol Oral Solution [10 mg/kg/Day]

Serious: 0/20 (0%)

Deaths: 0/20

Mid Dose Cannabidiol Oral Solution [20 mg/kg/Day]

Serious: 1/20 (5%)

Deaths: 0/20

High Dose Cannabidiol Oral Solution [40 mg/kg/Day]

Serious: 2/21 (10%)

Deaths: 0/21

Serious adverse events (3 terms)

Reaction	System	Low Dose Cannabidiol Oral …	Mid Dose Cannabidiol Oral …	High Dose Cannabidiol Oral…
Apnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Drug eruption	Skin and subcutaneous tissue disorders	—	—	—
Thrombophlebitis	Vascular disorders	—	—	—

Other adverse events (66 terms — click to expand)

Reaction	System	Low Dose Cannabidiol Oral …	Mid Dose Cannabidiol Oral …	High Dose Cannabidiol Oral…
Diarrhoea	Gastrointestinal disorders	—	—	—
Somnolence	Nervous system disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—
Psychomotor hyperactivity	Nervous system disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Catheter site pruritus	General disorders	—	—	—
Weight increased	Investigations	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Metabolic acidosis	Metabolism and nutrition disorders	—	—	—
Ataxia	Nervous system disorders	—	—	—
Dermatitis contact	Skin and subcutaneous tissue disorders	—	—	—
Pyrexia	General disorders	—	—	—
Seizure	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Ecchymosis	Skin and subcutaneous tissue disorders	—	—	—
Oral mucosal erythema	Gastrointestinal disorders	—	—	—
Oral pain	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Thirst	General disorders	—	—	—
Lice infestation	Infections and infestations	—	—	—
Skin abrasion	Injury, poisoning and procedural complications	—	—	—
Weight decreased	Investigations	—	—	—
Hypersomnia	Nervous system disorders	—	—	—
Syncope	Nervous system disorders	—	—	—
Aggression	Psychiatric disorders	—	—	—
Agitation	Psychiatric disorders	—	—	—
Irritability	Psychiatric disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Dermatitis	Skin and subcutaneous tissue disorders	—	—	—
Nodal rhythm	Cardiac disorders	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—
Injection site reaction	General disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Blood follicle stimulating hormone increased	Investigations	—	—	—
Hyperphosphataemia	Metabolism and nutrition disorders	—	—	—

Most-reported serious reactions: Apnoea, Drug eruption, Thrombophlebitis.

Data from ClinicalTrials.gov NCT02324673 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials.
   Silvestro S, Mammana S, Cavalli E, Bramanti P, et al · · 2019 · cited 114× · PMID 31013866 · DOI 10.3390/molecules24081459
2. Pharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy.
   Wheless JW, Dlugos D, Miller I, Oh DA, et al · · 2019 · cited 63× · PMID 31049885 · DOI 10.1007/s40263-019-00624-4
3. Beyond Pain Relief: A Review on Cannabidiol Potential in Medical Therapies.
   Luz-Veiga M, Azevedo-Silva J, Fernandes JC. · · 2023 · cited 15× · PMID 37259306 · DOI 10.3390/ph16020155
4. Medical Cannabis in Pediatric Oncology: Friend or Foe?
   Malach M, Kovalchuk I, Kovalchuk O. · · 2022 · cited 8× · PMID 35337156 · DOI 10.3390/ph15030359
5. Cannabinoids, Inner Ear, Hearing, and Tinnitus: A Neuroimmunological Perspective.
   Perin P, Mabou Tagne A, Enrico P, Marino F, et al · · 2020 · cited 8× · PMID 33329293 · DOI 10.3389/fneur.2020.505995
6. Drug-Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain.
   Campos MG, China M, Cláudio M, Capinha M, et al · · 2024 · cited 2× · PMID 38794183 · DOI 10.3390/ph17050613