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

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 <= 25 mg/kg or 450 mg, 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 12 weeks of treatment. Responders were those showing a 50% reduction from baseline monthly seizure frequency. Safety assessments monitored vital sips, 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 +/- 42 mg/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. (C) 2019 The Authors. Published by Elsevier Inc.