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Epilepsy Behav. 2019 Aug 5;98(Pt A):233-237. doi: 10.1016/j.yebeh.2019.07.007. [Epub ahead of print]

The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study.

Author information

1
Pediatric Neurology Center, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel. Electronic address: alexism@tlvmc.gov.il.
2
Pediatric Neurology Center, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
3
Pediatric Neurology Center, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Israel.
4
BioStats Statistical Consulting, Modiin, Israel.
5
PhytoTech Therapeutics, Tel-Aviv, Israel.

Abstract

INTRODUCTION:

Several works have reported on the antiepileptic impact of cannabis-based preparations in patients with treatment-resistant epilepsy (TRE). However, current formulations suffer from low bioavailability and side effects. PTL-101, an oral formulation containing highly purified cannabidiol (CBD) embedded in seamless gelatin matrix beadlets was designed to enhance bioavailability and maintain a constant gastrointestinal transit time.

METHODS:

This phase II, prospective study was open to pediatric patients with TRE on stable antiepileptic drugs' (AEDs) doses, who experienced ≥4 seizures within four weeks of enrolment and with a history of ≥4 AEDs failing to provide seizure control. Following a 4-week observation period, patients began a 2-week dose-titration phase (up to ≤25mg/kg or 450mg, the lower of the two), followed by a 10-week maintenance treatment period. Caregivers recorded seizure frequency, type, and severity and ranked their global impressions after 7 and 12weeks of treatment. Responders were those showing a ≥50% reduction from baseline monthly seizure frequency. Safety assessments monitored vital signs, adverse effects, physical and neurological exams, and laboratory tests.

RESULTS:

Sixteen patients (age: 9.1±3.4) enrolled in the study; 11 completed the full treatment program. The average maintenance dose was 13.6±4.2mg/kg. Patient adherence to treatment regimens was 96.3±9.9%. By the end of the treatment period, 81.9% and 73.4±24.6% (p<0.05) reductions from baseline median seizure count and monthly seizure frequency, respectively, were recorded. Responders' rate was 56%; two patients became fully seizure-free. By study end, 8 (73%) caregivers reported an improved/very much improved condition, and 9 (82%) reported reduced/very much reduced seizure severity. Most commonly reported treatment-related adverse effects were sleep disturbance/insomnia, (4 (25.0%) patients), followed by somnolence, increased seizure frequency, and restlessness (3 patients each (18.8%)). None were serious or severe, and all resolved.

CONCLUSIONS:

PTL-101 was safe and tolerable for use and demonstrated a potent seizure-reducing effect among pediatric patients with TRE.

KEYWORDS:

Cannabidiol; Cannabinoids; Clinical study; Intractable epilepsy; Oral drug delivery; Pediatric

PMID:
31394352
DOI:
10.1016/j.yebeh.2019.07.007
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