Studie CLARINET dnes představuje nejsilnější randomizovanou studii zabývající se antiproliferačním efektem somatostatinových analog u pacientů s neuroendokrinními nádory. Základní studie CLARINET zahrnula 204 nemocných: pacienti měli dobře/středně diferencované nefunkční enteropankreatické neuroendokrinní tumory s proliferačním indexem Ki-67 < 10 %, v předchozích šesti měsících jim nebyla podávána žádná léková terapie, byl u nich dokumentován stav PD/SD (progressive disease/stable disease) a dostávali lanreotid nebo placebo po dobu 96 týdnů až do doby, než došlo k progresi onemocnění (dle kritérií RECIST 1.0) nebo k úmrtí. Open-label extenze (OLE) studie CLARINET zahrnula 88 nemocných: pacienti vstoupili do OLE studie, pokud měli SD na konci základní studie nebo pokud vykazovali PD při podávání placeba během základní studie; lanreotid byl podáván do doby, než došlo k další progresi onemocnění nebo k úmrtí nemocného. Medián PFS (času od randomizace k první progresi onemocnění v základní studii nebo v její OLE) při léčbě lanreotidem byl 32,8 měsíce. Medián PFS při podávání placeba v základní studii do další progrese při léčbě lanreotidem v OLE studie byl 14 měsíců. Bezpečnostní profily byly podobné ve všech podskupinách. V obou fázích studie nebyla identifikována žádná nová bezpečnostní rizika.

Today, the CLARINET study is the most powerful randomized study exploring the antiproliferative effect of somatostatin analogues in neuroendocrine tumours. The CLARINET core study (n = 204): patients had metastatic well/moderately differentiated non-functioning enteropancreatic neuroendocrine tumours with proliferative index Ki-67 < 10%, no prior medical therapy within 6 months, documented PD/SD (progressive disease/stable disease) status, and received lanreotid or placebo for 96 weeks or until PD (RECIST 1.0) or death. Open-label extension, OLE (n = 88): patients entered the OLE if they hod SD at the end of the core study or they had PD on placebo during the core study; lanreotid is administered until (further) PD or death. Median progression free survival, PES (time from randomisation to first PD in core or OLE) on lanreotid was 32.8 months. Median time from first PD on acebo (core) to further PD on lanreotid (OLE): 14.0 months (i.e., 2nd progression). Safety profiles were similar in subgroups. No new safety concerns were identified in any population.

• Keywords
• lanreotid autogel,
• MeSH
• Survival Analysis MeSH
• Peptides, Cyclic therapeutic use   MeSH
• Drug Evaluation * statistics & numerical data   MeSH
• Humans MeSH
• Neoplasm Metastasis drug therapy   MeSH
• Digestive System Neoplasms etiology   drug therapy   mortality   MeSH
• Neuroendocrine Tumors * etiology   drug therapy   mortality   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Somatostatin * analogs & derivatives   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) treated with PRM-151, a recombinant human pentraxin 2 protein, in a phase 2 double-blind, randomised controlled trial had significantly reduced decline in percentage of predicted forced vital capacity (FVC) and stabilised 6-min walking distance compared with placebo over a 28-week period. Here we report the 76-week results of an open-label extension study. METHODS: Patients who completed the 28-week double-blind period of the PRM-151-202 trial were eligible to participate in the open-label extension study. Patients previously enrolled in the PRM-151 group continued this treatment and those previously in the placebo group crossed over to PRM-151. All patients received PRM-151 in 28-week cycles with loading doses of 10 mg/kg by 60 min intravenous infusions on days 1, 3, and 5 in the first week of each cycle followed by one infusion of 10 mg/kg every 4 weeks. The primary objective of the open-label extension study was to assess the long-term safety and tolerability of PRM-151, which were assessed by analysing adverse events (AEs) up to week 76 in all patients who received at least one dose of PRM-151 during the open-label extension study. Exploratory efficacy analyses were done by assessing changes from baseline in percentage of predicted FVC and 6-min walking distance, with descriptive statistics to week 76 and with random-intercept mixed models to week 52. This study is registered with ClinicalTrials.gov, number NCT02550873, and with EudraCT, number 2014-004782-24. FINDINGS: Of 116 patients who completed the double-blind treatment period, 111 entered the open-label extension study (74 from the PRM-151 group and 37 from the placebo group). 84 (76%) of 111 patients received concomitant IPF therapy (pirfenidone n=55 or nintedanib n=29). AEs were consistent with long-term IPF sequelae. 31 (28%) patients had serious AEs. Those occurring in two or more patients were pneumonia (six [5%] of 111), IPF exacerbation (four [4%]), IPF progression (four [4%]), and chest pain (two [2%]). 21 (19%) patients had severe AEs, of which IPF exacerbation and IPF progression each occurred in two (2%) patients. Two (2%) patients experienced life-threatening AEs (one had pneumonia and one had small-cell lung cancer extensive stage). A persistent treatment effect was observed for PRM-151 in patients who continued treatment, with a decline in percentage of predicted FVC of -3·6% per year and in 6-min walking distance of -10·5 m per year at week 52. In patients who started PRM-151 during the open-label extension study, compared with the slopes for placebo, decline reduced for percentage of predicted FVC (from -8·7% per year in weeks 0-28 to -0·9% per year in weeks 28-52, p<0·0001) and 6-min walking distance (from -54·9 m per year to -3·5 m per year, p=0·0224). INTERPRETATION: Long-term treatment with PRM-151 was well tolerated and the effects on percentage of predicted FVC and 6-min walking distance were persistent on continuation and positive in patients who crossed over from placebo. These findings support further study of PRM-151 in larger populations of patients with IPF. FUNDING: Promedior.

• MeSH
• Long-Term Care MeSH
• Double-Blind Method MeSH
• Homeodomain Proteins therapeutic use   MeSH
• Idiopathic Pulmonary Fibrosis drug therapy   MeSH
• Cross-Over Studies MeSH
• Humans MeSH
• Recombinant Proteins therapeutic use   MeSH
• Aged MeSH
• Serum Amyloid P-Component therapeutic use   MeSH
• Vital Capacity MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

PURPOSE: In the phase III CLARINET study (NCT00353496), lanreotide autogel/depot (lanreotide) significantly improved progression-free survival (PFS) vs placebo in patients with non-functioning intestinal or pancreatic neuroendocrine tumours (NETs). The aim of CLARINET open-label extension (OLE) (NCT00842348) was to evaluate long-term safety and efficacy of lanreotide in these patients. METHODS: Patients from the CLARINET study were eligible for the OLE if they had stable disease (irrespective of treatment group) or progressive disease (PD) (placebo-treated patients only). All patients in the OLE received lanreotide 120 mg every 28 days. Computed tomography or magnetic resonance imaging scans were conducted every 6 months and assessed locally for PD (the final scan was also assessed centrally). RESULTS: Overall, 89 patients took part in the OLE (lanreotide, n = 42; placebo, n = 47). Median (range) exposure to lanreotide in patients who received lanreotide in the core study and OLE (LAN-LAN group) was 59.0 (26.0-102.3) months. In this group, the overall incidences of adverse events (AEs) and treatment-related AEs were lower in the OLE than in the core study. Median [95% CI] PFS in the LAN-LAN group was 38.5 [30.9; 59.4] months. In placebo-treated patients with PD at the end of the core study, time to death or subsequent PD during the OLE was 19 [10.1; 26.7] months. CONCLUSIONS: This study provides new evidence on the long-term safety profile and sustained anti-tumour effects of lanreotide autogel/depot in indolent and progressive metastatic intestinal or pancreatic NETs.

• MeSH
• Peptides, Cyclic therapeutic use   MeSH
• Humans MeSH
• Pancreatic Neoplasms * drug therapy   MeSH
• Neuroendocrine Tumors * drug therapy   MeSH
• Antineoplastic Agents * adverse effects   MeSH
• Somatostatin analogs & derivatives   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs.

• MeSH
• Peptides, Cyclic adverse effects   therapeutic use   MeSH
• Humans MeSH
• Pancreatic Neoplasms drug therapy   MeSH
• Neuroendocrine Tumors drug therapy   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Somatostatin adverse effects   analogs & derivatives   therapeutic use   MeSH
• Intestinal Neoplasms drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Galcanezumab, a monoclonal antibody to calcitonin gene-related peptide, was found to be safe and efficacious for the preventive treatment of chronic migraine based on the randomized, placebo-controlled double-blind period of the REGAIN study. Long-term safety and efficacy were assessed in an open-label extension. METHODS: Patients 18-65 years old with chronic migraine completing the 3-month double-blind period of REGAIN could enter a 9-month open-label extension (OLE; months 4-12). Upon entering the OLE, patients received a 240-mg galcanezumab loading dose, then 120 mg at the next month, with flexible dosing thereafter (120 or 240 mg/month). The primary efficacy measure was the mean change in the number of monthly migraine headache days from double-blind baseline to month 12. Other endpoints included response rates (based on percent reduction in monthly migraine headache days from double-blind baseline to month 12), safety and tolerability. RESULTS: Of patients who completed double-blind treatment, 1022 (99%) entered the OLE, with 81% completing month 12. From a baseline of 19.4 monthly migraine headache days at the beginning of the double-blind period, patients at month 12 in the previous placebo, 120-mg, and 240-mg galcanezumab groups had a mean change of -8.5, -9.0, and -8.0, respectively (SE = 0.43 to 0.55, within-group p's < .001). At month 12, the percentage of patients with ≥50% response was 57%, 57%, and 53%, respectively. Percentage with ≥75% response was 32%, 31%, and 30%, respectively. Percentage with 100% response was 8%, 6%, and 6%, respectively. There were no significant new safety findings during the open-label period. The incidence of discontinuation from the OLE due to adverse events was 5%. CONCLUSION: Galcanezumab was effective, safe, and well-tolerated, with high adherence, for up to 12 months of treatment in patients with chronic migraine. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02614261; www.clinicaltrials.gov/ct2/show/NCT02614261.

• MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Antibodies, Monoclonal, Humanized adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Migraine Disorders * drug therapy   prevention & control   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Antibodies, Monoclonal therapeutic use   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: ABP 501 was evaluated in a phase 3 single-arm, open-label extension (OLE) study to collect additional safety and efficacy data in patients with rheumatoid arthritis (RA). METHODS: Subjects completing the final visit in the parent phase 3 randomized, double-blind, controlled equivalence study comparing the efficacy and safety of the biosimilar ABP 501 with adalimumab reference product (RP) were enrolled in this open-label extension (OLE) study. All subjects received 40 mg ABP 501 every other week for 68 weeks. Key safety endpoints included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and anti-drug antibody (ADA) incidences. Efficacy endpoints included ACR20 (at least 20% improvement in American College of Rheumatology core set measurements from baseline) and Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP) change from baseline. RESULTS: Among 466/467 patients treated with ABP 501, 229 transitioned from the ABP 501 arm of the parent study (ABP 501/ABP 501) and 237 from the adalimumab RP arm (RP/ABP 501); 412/467 (88.2%) patients completed the study. The overall TEAE incidence was 63.7% (297/466); grade ≥ 3 TEAE incidence was 9.0% (42/466). The incidence of TEAEs leading to discontinuation of investigational product was 3.6% (17/466). The SAE incidence was 9.9% (46/466). Overall, 18.2% (85/466) of subjects developed binding ADAs and 6.9% (32/466) developed neutralizing ADAs in the OLE study. The ACR20 response rate was 73.3% (340/464 subjects) at OLE baseline, and 78.8% (327/415 subjects) at week 70 of the OLE study. The overall mean DAS28-CRP change from the parent study baseline was - 2.25 at the OLE study baseline (n = 440), - 2.36 at week 4 (n = 463), - 2.41 at week 24 (n = 450), - 2.55 at week 48 (n = 433), and - 2.60 at week 70 (n = 412). Efficacy was maintained throughout the study. CONCLUSIONS: Efficacy previously demonstrated in the parent study was maintained in this OLE study with no new safety findings. Long-term safety, immunogenicity, and efficacy were similar in the ABP 501/ABP 501 and RP/ABP 501 groups. The single switch from RP to ABP 501 did not impact immunogenicity. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02114931.

• MeSH
• Adalimumab adverse effects   therapeutic use   MeSH
• Antirheumatic Agents adverse effects   therapeutic use   MeSH
• Biosimilar Pharmaceuticals adverse effects   therapeutic use   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Nasopharyngitis chemically induced   MeSH
• Arthritis, Rheumatoid drug therapy   MeSH
• Drug Administration Schedule MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: This study reports the long-term safety and efficacy of erenumab in chronic migraine patients. METHODS: This was a 52-week open-label extension study of a 12-week double-blind treatment phase study. During the double-blind treatment phase, patients received placebo or once-monthly erenumab 70 mg or 140 mg. During the open-label treatment phase, the initial monthly dose was erenumab 70 mg. Following protocol amendment, patients continued to receive erenumab 70 mg if they had already completed their Week 28 visit, otherwise, patients switched from 70 mg to 140 mg; if enrolled after the amendment, patients received 140 mg monthly throughout. RESULTS: In all, 451/609 (74.1%) enrolled patients completed the study. The exposure-adjusted patient incidence rate for any adverse event was 126.3/100 patient-years for the overall erenumab group. Overall, the adverse event profile was similar to that observed in the double-blind treatment phase. Adverse event incidence rates did not increase with long-term erenumab treatment compared with the double-blind treatment phase, and no new serious or treatment-emergent events were seen. Efficacy was sustained throughout the 52 weeks. Clinically significant reductions from double-blind treatment phase baseline (about half) were observed for monthly migraine days and migraine-specific medication days. Achievement of ≥50%, ≥75% and 100% reductions from the double-blind treatment phase baseline in monthly migraine days at Week 52 were reported by 59.0%, 33.2% and 8.9% of patients, respectively, for the combined dose group. A numerically greater benefit was observed with 140 mg compared with 70 mg at Weeks 40 and 52. CONCLUSIONS: Sustained efficacy of long-term erenumab treatment in patients with chronic migraine is demonstrated, with safety results consistent with the known safety profile of erenumab and adverse event rates comparable to placebo adverse event rates in the double-blind treatment phase. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT02174861).

• MeSH
• Calcitonin Gene-Related Peptide Receptor Antagonists therapeutic use   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Migraine Disorders drug therapy   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: Daclizumab is a humanized monoclonal antibody against CD25 that modulates interleukin 2 signaling. The SELECT TRILOGY of clinical studies (SELECT/SELECTION/SELECTED) evaluated the safety and efficacy of daclizumab in patients with relapsing-remitting multiple sclerosis (RRMS). We report the long-term safety and efficacy of daclizumab 150 mg subcutaneous every 4 weeks in patients with RRMS in the SELECTED open-label extension study. METHODS: An interim intent-to-treat analysis of all enrolled patients was performed in January 2014 for this ongoing study. RESULTS: The SELECTED study enrolled 90% of patients who completed SELECTION. In the safety and efficacy analysis (N = 410), median treatment time in SELECTED was 25 months (range, <1-45). Adverse events (AEs) were reported in 76% of patients, serious AEs (SAEs) excluding MS relapse in 16%, and treatment discontinuation due to AEs including multiple sclerosis (MS) relapse in 12%. AEs were primarily of mild to moderate severity, and common AEs (≥10%), excluding MS relapse, were nasopharyngitis (12%) and upper respiratory tract infection (12%). Most commonly reported SAEs (in ≥3 patients), excluding MS relapses, were increased serum hepatic enzymes, pneumonia, ulcerative colitis, and urinary tract infection (<1% each). Incidences of AE groups of interest include cutaneous events (28%), cutaneous SAEs (2%), gastrointestinal SAEs (2%), hepatic SAEs, (1%) and malignancies (1%). The incidence of AEs, SAEs, and treatment-related study discontinuations did not increase over time and no deaths were reported. The adjusted annualized relapse rate (95% confidence interval (CI)) analyzed at 6-month intervals was 0.15 (0.10-0.22) for weeks 97-120 and 0.15 (0.10-0.21) for weeks 121-144. In year 3, the adjusted mean (95% CI) number of new/newly enlarging T2 hyperintense lesions was 1.26 (0.93-1.72) and the mean (median) annualized change in brain volume was -0.32% (-0.34%). CONCLUSIONS: The AE incidence did not increase with extension of therapy into year 3 in SELECTED; the safety profile was similar to that previously observed. The clinical efficacy of daclizumab was sustained over the 3 years comprising the SELECT TRILOGY, although potential selection bias cannot be excluded. TRIAL REGISTRATION: Clinicaltrials.gov NCT01051349; first registered January 15, 2010.

• MeSH
• Alanine Transaminase drug effects   MeSH
• Intention to Treat Analysis MeSH
• Aspartate Aminotransferases drug effects   MeSH
• Safety MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   adverse effects   therapeutic use   MeSH
• Immunoglobulin G administration & dosage   adverse effects   therapeutic use   MeSH
• Immunosuppressive Agents administration & dosage   adverse effects   therapeutic use   MeSH
• Respiratory Tract Infections chemically induced   MeSH
• Urinary Tract Infections chemically induced   MeSH
• Injections, Subcutaneous MeSH
• Cohort Studies MeSH
• Drug Eruptions etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Brain drug effects   MeSH
• Follow-Up Studies MeSH
• Nasopharyngitis chemically induced   MeSH
• Pneumonia chemically induced   MeSH
• Interleukin-2 Receptor alpha Subunit administration & dosage   therapeutic use   MeSH
• Recurrence MeSH
• Multiple Sclerosis, Relapsing-Remitting drug therapy   MeSH
• Colitis, Ulcerative chemically induced   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

BACKGROUND AND AIMS: Lysosomal acid lipase deficiency is characterized by hepatomegaly and dyslipidaemia, which can lead to cirrhosis and premature atherosclerosis. Sebelipase alfa is an approved recombinant human lysosomal acid lipase. In an open-label extension study of adults with lysosomal acid lipase deficiency (LAL-CL04), sebelipase alfa treatment for 1 year reduced serum transaminase levels and liver fat content and improved serum lipid levels. METHODS: Final data from LAL-CL04 are reported herein for patients who received sebelipase alfa infusions (1.0 or 3.0 mg/kg every other week) for up to 5 years. RESULTS: Of 8 patients enrolled, 7 received sebelipase alfa for 224-260 weeks; 1 was lost to follow-up. Median baseline levels of alanine aminotransferase and aspartate aminotransferase (81.5 and 50.0 U/L, respectively) were decreased through the end-of-study visit (54.0 and 34.0 U/L). Median low-density lipoprotein cholesterol decreased from 113 to 78 mg/dL, total cholesterol decreased from 171 to 132 mg/dL, and high-density lipoprotein cholesterol increased from 37 to 42 mg/dL. Most treatment-emergent adverse events were nonserious (99%), mild/moderate (98%) and unrelated to sebelipase alfa (87%); no patient discontinued as a result of treatment-emergent adverse events. One patient had 2 serious treatment-emergent adverse events (cholecystitis and cholelithiasis; assessed as unlikely related to sebelipase alfa). Two patients had 20 nonserious infusion-associated reactions in weeks 6-38; all were manageable. One patient tested positive for antidrug antibodies (single occurrence). CONCLUSIONS: Sebelipase alfa was well tolerated and improved serum transaminase and lipid levels for up to 5 years in adults with lysosomal acid lipase deficiency. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov record NCT01488097.

• MeSH
• Alanine Transaminase MeSH
• Adult MeSH
• Humans MeSH
• Sterol Esterase * MeSH
• Wolman Disease * drug therapy   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVE: This post hoc analysis evaluated long-term efficacy and safety in patients with focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who entered open-label extension (OLEx) studies to receive long-term adjunctive perampanel. METHODS: Patients aged 12 years and older who completed phase II or III randomized, double-blind, placebo-controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open-label maintenance period (32-424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed. RESULTS: Baseline characteristics were generally balanced between patients with FBTCS (n = 720) and GTCS (n = 138). Mean (standard deviation) cumulative duration of perampanel exposure was 102.3 (70.3) weeks (FBTCS) and 83.9 (38.4) weeks (GTCS). Retention rates were 50.0% for up to 4 years (FBTCS) and 49.2% for up to 2 years (GTCS). Across OLEx treatment durations, median reductions in seizure frequency per 28 days were 66.7% (FBTCS) and 80.6% (GTCS). Fifty percent and 75% responder and seizure-freedom rates were 59.5%, 45.3%, and 18.4%, respectively (FBTCS), and 72.5%, 51.5%, and 16.7%, respectively (GTCS). Efficacy was sustained for up to 4 years (FBTCS) and up to 3 years (GTCS), even when accounting for early dropouts. TEAE incidence was highest during Year 1 (FBTCS, 85.3%; GTCS, 86.2%); most common were dizziness and somnolence. During Year 1, serious TEAEs were reported in 81 (11.3%; FBTCS) and 10 (7.2%; GTCS) patients. TEAEs were consistent with the known safety profile of perampanel; no new safety signals were identified with long-term treatment. SIGNIFICANCE: This post hoc analysis suggests long-term (up to 4 years) adjunctive perampanel (up to 12 mg/d) is efficacious and well tolerated in patients (aged 12 years and older) with FBTCS or GTCS.

• MeSH
• Anticonvulsants administration & dosage   adverse effects   MeSH
• Time Factors MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Drug Therapy, Combination MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Pyridones administration & dosage   adverse effects   MeSH
• Sleepiness MeSH
• Treatment Outcome MeSH
• Seizures diagnosis   drug therapy   epidemiology   MeSH
• Dizziness chemically induced   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH