Long-Term Safety, Efficacy of Add-on Cannabidiol (CBD) for Treatment of Tuberous Sclerosis Complex-Associated Seizures in an Open-Label Extension

2021 ◽  
Author(s):  
F. Sahebkar ◽  
E. M. Bebin ◽  
F. Filloux ◽  
F. E. Jansen ◽  
P. Kwan ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Open Label ◽  
Open Label Extension

scholarly journals Long‐term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: An open‐label extension trial

Epilepsia ◽  
2021 ◽  
Author(s):  
Elizabeth A. Thiele ◽  
E. Martina Bebin ◽  
Francis Filloux ◽  
Patrick Kwan ◽  
Rachael Loftus ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Open Label ◽  
Open Label Extension ◽  
Extension Trial

scholarly journals Long-Term Exposure and Safety of a Novel Topical Rapamycin Cream for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex: Results From a Single-Center, Open-Label Trial

2019 ◽  
Vol 6 ◽  
pp. 2329048X1983504
Author(s):  
Margaret C. Wheless ◽  
Apana A. Takwi ◽  
Hassan Almoazen ◽  
James W. Wheless
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Fibrous Tissue ◽  
Systemic Absorption ◽  
Topical Formulation ◽  
Open Label ◽  
Long Term Follow Up ◽  
The Face ◽  
Systemic Side Effects

Facial angiofibromas, composed of fibrous tissue and blood vessels appearing on the face, are closely associated with tuberous sclerosis complex. Historically, oral rapamycin, a mammalian target of the rapamycin inhibitor of cell proliferation, has been used to treat visceral tuberous sclerosis–related tumors; however, the side effect profile of this medicine generally precludes its use in patients lacking significant internal involvement. The authors developed a novel topical formulation of rapamycin cream to treat the facial angiofibroma without exposing patients to possible systemic side effects. We followed 11 patients in a long-term, open-label, prospective study to evaluate the safety and effectiveness of rapamycin cream when used chronically. All of the patients showed an improvement in the appearance of their facial angiofibroma which was maintained in long-term follow-up without safety concerns or systemic absorption. The novel rapamycin cream was tolerated well by all patients and represents a way to address the cutaneous manifestation of tuberous sclerosis complex.

scholarly journals Everolimus for treatment-refractory seizures in TSC

2018 ◽  
Vol 8 (5) ◽  
pp. 412-420 ◽  
Author(s):  
David N. Franz ◽  
John A. Lawson ◽  
Zuhal Yapici ◽  
Hiroko Ikeda ◽  
Tilman Polster ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Open Label ◽  
Median Percentage ◽  
The Core ◽  
Open Label Extension ◽  
Core Phase ◽  
Refractory Seizures ◽  
Treatment Refractory ◽  
Over Time

BackgroundEXamining everolimus In a Study of Tuberous sclerosis 3 (EXIST-3) demonstrated significantly reduced seizure frequency (SF) with everolimus vs placebo. In this study, we evaluate the long-term efficacy and safety of everolimus for tuberous sclerosis complex (TSC)-associated treatment-refractory seizures.MethodsAfter completion of the core phase, patients could enter an open-label extension phase and receive everolimus (target exposure, 3–15 ng/mL) for ≥48 weeks. Efficacy end points included change from baseline in average weekly SF expressed as response rate (RR, ≥50% reduction) and median percentage reduction (PR).ResultsOf 366 patients, 361 received everolimus in core/extension phases. The RR was 31% (95% CI, 26.2–36.1; N = 352) at week 18, 46.6% (95% CI, 40.9–52.5; N = 298) at 1 year, and 57.7% (95% CI, 49.7–65.4; N = 163) at 2 years. Median PR in SF was 31.7% (95% CI, 28.5–36.1) at week 18, 46.7% (95% CI, 40.2–54) at 1 year, and 56.9% (95% CI, 50–68.4) at 2 years. Ninety-five patients (26.3%) discontinued everolimus before 2 years; 103 (28.5%) had <2 years of follow-up at study cutoff, and 40% were exposed to everolimus for ≥2 years. An analysis classifying discontinued patients as nonresponders showed an RR of 30.2% (95% CI, 25.5–35.2; N = 361) at week 18, 38.8% (95% CI, 33.7–44.1; N = 358) at 1 year, and 41% (95% CI, 34.6–47.7; N = 229) at 2 years, suggesting sustained benefit over time. The incidence of grade 3/4 adverse events (AEs) (any cause) was 40.2%, and 13% discontinued because of AEs (pneumonia [1.7%] and stomatitis [1.4%]). Two deaths were suspected to be treatment-related (pneumonia and septic shock).ConclusionsSustained reductions in TSC-associated treatment-refractory seizures over time were achieved with adjunctive everolimus. The safety profile was consistent with the core phase with no new safety concerns.Classification of evidenceThis study provides Class IV evidence that long-term everolimus therapy reduces SF in patients with TSC-associated treatment-refractory seizures.

scholarly journals Effects of bumetanide on neurodevelopmental impairments in patients with tuberous sclerosis complex: an open-label pilot study

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dorinde M. van Andel ◽  
Jan J. Sprengers ◽  
Bob Oranje ◽  
Floortje E. Scheepers ◽  
Floor E. Jansen ◽  
...  
Keyword(s):  
Pilot Study ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Open Label

scholarly journals Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001649
Author(s):  
John B Buse ◽  
Bruce W Bode ◽  
Ann Mertens ◽  
Young Min Cho ◽  
Erik Christiansen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Dose Adjustment ◽  
Main Phase ◽  
Open Label ◽  
Open Label Extension ◽  
Registration Number ◽  
Flexible Dose

IntroductionThe PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide.Research design and methodsA 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA1c) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA1c and body weight.ResultsIn the durability part, mean (SD) changes in HbA1c and body weight from week 0 were –1.5% (0.8) and –1.3% (1.0) and –2.8 kg (3.8) and –3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA1c from week 52 to week 104 were –0.2% for oral semaglutide and 0.1% for sitagliptin (difference –0.3% (95% CI –0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA1c <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were –2.4 kg and –0.9 kg (difference –1.5 kg (95% CI –2.8 to –0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide.ConclusionsLong-term oral semaglutide with flexible dose adjustment maintained HbA1c reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight.Trial registration numberNCT02849080.

scholarly journals Long‐term safety and efficacy of add‐on cannabidiol in patients with Lennox–Gastaut syndrome: Results of a long‐term open‐label extension trial

Epilepsia ◽  
2021 ◽  
Author(s):  
Anup D. Patel ◽  
Maria Mazurkiewicz‐Bełdzińska ◽  
Richard F. Chin ◽  
Antonio Gil‐Nagel ◽  
Boudewijn Gunning ◽  
...  
Keyword(s):  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Extension Trial
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