Alexis Mitelpunkt, MDAlexis Mitelpunkt, MD
Investigational oral capsules containing highly purified cannabidiol have shown promising results in a phase 2, open-label study in patients with treatment-resistant epilepsy.1

The formulation, PTL-101 (CBD GelPell; Satipharm Ltd.), was examined for safety and efficacy as an adjunctive treatment for the reduction of seizure frequency. The product, which contains a novel formulation of purified cannabidiol encased in a gelatin bead which is then placed in a gastro-resistant capsule, is currently available in the United Kingdom and Australia.2

The single-center trial (NCT02987114) included 16 pediatric patients with treatment-resistant epilepsy, 11 of whom completed the full treatment program. Patients were eligible for inclusion if they were on stable antiepileptic drug (AED) doses, had ≥4 seizures within 4 weeks of study enrollment, and had a history of ≥4 failed AEDs for seizure control. The study included a 4-week observation period, followed by a 2-week dose titration period (up to ≤25 mg/kg or 450 mg, the lower of the 2), and a 10-week maintenance treatment phase. Caregivers were asked to record seizure frequency, severity, and type and rank their global impressions after weeks 7 and 12.

Patients (age 2-15) received capsules containing either 50 mg or 100 mg cannabidiol twice daily (for higher doses only). Responders were considered those who demonstrated a ≥50% reduction in monthly seizure frequency from baseline. Primary end points were incidence of treatment-related adverse events (AEs) and percent change in mean monthly seizure frequency.

Overall, researchers observed an 81.9% reduction in median seizure count and 73.4% decline in monthly seizure frequency at 12 weeks (P <.05). Fifty-six percent of the study population were considered responders, with 2 patients becoming seizure-free by the end of the treatment period. At the conclusion of the study, 73% of caregivers reported conditions to be improved/very much improved, and 82% reported that seizure severity was reduced/very much reduced. Notably, the average maintenance phase starting dose was 15.4±5.1 mg/kg, while the average dose for the 10-week maintenance phase was 13.6±4.2 mg/kg.

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The most common AEs reported were sleep disturbance/insomnia (25%), as well as somnolence, increased seizure frequency, and restlessness (all 18.8%). No AEs were considered serious or severe and all were resolved. Ultimately, 2 patients discontinued treatment due to seizure worsening, one of which was related to poor treatment adherence, and the other for what was likely treatment-related mild AEs, including an increase in drop attacks, aggression, and insomnia. One patient withdrew consent. Overall patient adherence to the treatment was 96.3%±9.9%.

“These clinical measures translated to meaningful improvements in the condition, as expressed by caregivers' global impressions of significant overall improvements and of marked reductions in seizure severity,” the researchers wrote.1 “Despite the predefined dose limitation and consequently relatively low PTL-101 doses administered in this study, its therapeutic impact was similar to those reported for other oral CBD preparations.”

Importantly, the investigators noted that there were no lab findings of elevated liver enzymes—an AE observed in other investigations of oral cannabidiol products and grounds for treatment withdrawal.

Additional placebo-controlled, blinded studies with larger study populations are required to confirm the safety and efficacy of PTL-101.
REFERENCES
1. Mitelpunkt A, Kramer U, Kedem Hausman M, et al. The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study. Epilepsy Behav. 2019;(98)233-237.
2. Havest One phase II clinical trials on Satipharm CBD GelPell published in peer-reviewed journal [news release]. Vancouver: Harvest One Inc. August 13, 2019. prnewswire.com/news-releases/harvest-one-phase-ii-clinical-trials-on-satipharm-cbd-gelpell-published-in-peer-reviewed-medical-journal-300900513.html. Accessed August 13, 2019.