Study register · detailKlinische Studie · Epilepsy · 2019
The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study.
Mitelpunkt et al.·Epilepsy & behaviorImpact 2.4
Clear benefitGRADEModerate61 citations
Samplen = 16 Pat.
Duration4-week observation phase…
EndpointMonthly seizure frequency
Blindingoffen
DesignKlinische Studie
Cannabinoidcbd
Max. dose450.0 mg
Routeoral
”Key finding
PTL-101 led to a 73,4% reduction in monthly seizure frequency, 56% of patients were responders (≥50% reduction), and two patients became seizure-free.
Summary
Phase II open-label study (n=16, children with treatment-refractory epilepsy) on PTL-101 (oral CBD in gelatin matrix beadlets). Age 9,1±3,4 years, mean maintenance dose 13,6±4,2 mg/kg. 11 patients completed treatment (12 weeks). Median seizure count -81,9% from baseline, monthly seizure frequency -73,4±24,6% (p<0,05). Responder rate (≥50% reduction) 56%; 2 patients seizure-free. 73% of caregivers reported improved/greatly improved condition, 82% reduced/greatly reduced seizure severity. Most common adverse events: sleep disturbances/insomnia (25%), somnolence, increased seizure frequency, restlessness.
P
PopulationPediatric patients with treatment-resistant epilepsy (≥4 seizures/4 weeks, ≥4 prior AED failures), n=16, mean age 9,1 years
I
InterventionPTL-101 (oral cannabidiol in gelatin matrix beadlets), dose titration up to ≤25 mg/kg or 450 mg/day, mean maintenance dose 13,6 mg/kg
O
OutcomeReduction in median seizure frequency by 81,9% (seizure count) or 73,4% (monthly seizure frequency, p<0,05) versus baseline; responder rate 56%; 2 patients seizure-free
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingOpen-label
Effect sizeClear benefit
Citations / year★★★★★
Authors
Mitelpunkt A, Kramer U, Hausman Kedem M, Zilbershot Fink E, Orbach R, Chernuha V, Fattal-Valevski A, Deutsch L, Heffetz D, Sacks H
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.