Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study

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)

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A randomized, double-blind, placebo-controlled trial and open-label extension study to evaluate the efficacy and safety of pregabalin in the treatment of neuropathic pain associated with human immunodeficiency virus neuropathy

Pain ◽

10.1016/j.pain.2014.05.027 ◽

2014 ◽

Vol 155 (10) ◽

pp. 1943-1954 ◽

Cited By ~ 30

Author(s):

David M. Simpson ◽

Andrew S.C. Rice ◽

Birol Emir ◽

Jaren Landen ◽

David Semel ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Neuropathic Pain ◽

Controlled Trial ◽

Extension Study ◽

Efficacy And Safety ◽

Open Label ◽

Double Blind ◽

Double Blind Placebo ◽

Immunodeficiency Virus ◽

Open Label Extension

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Evidence for safety and efficacy of risedronate in men with osteoporosis over 4years of treatment: Results from the 2-year, open-label, extension study of a 2-year, randomized, double-blind, placebo-controlled study

Bone ◽

10.1016/j.bone.2012.06.016 ◽

2012 ◽

Vol 51 (3) ◽

pp. 383-388 ◽

Cited By ~ 17

Author(s):

Steven Boonen ◽

Roman S. Lorenc ◽

Dietrich Wenderoth ◽

Karen J. Stoner ◽

Rachelle Eusebio ◽

...

Keyword(s):

Extension Study ◽

Controlled Study ◽

Treatment Results ◽

Open Label ◽

Double Blind ◽

Safety And Efficacy ◽

Double Blind Placebo ◽

Open Label Extension

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Long-term safety and effectiveness of lurasidone in schizophrenia: a 22-month, open-label extension study

CNS Spectrums ◽

10.1017/s1092852915000917 ◽

2016 ◽

Vol 21 (5) ◽

pp. 393-402 ◽

Cited By ~ 14

Author(s):

Christoph U. Correll ◽

Josephine Cucchiaro ◽

Robert Silva ◽

Jay Hsu ◽

Andrei Pikalov ◽

...

Keyword(s):

Controlled Trial ◽

Term Treatment ◽

Extension Study ◽

Open Label ◽

Double Blind ◽

Syndrome Scale ◽

Long Term Treatment ◽

Open Label Extension ◽

The Mean

ObjectiveTo evaluate the safety and effectiveness of lurasidone in the long-term treatment of patients with schizophrenia.MethodsPatients who completed a 6-week, double-blind (DB), placebo-controlled trial continued in a 22-month, open-label (OL) study during which they received once-daily, flexible-doses of lurasidone, 40–120 mg. Change in the Positive and Negative Syndrome Scale (PANSS) was analyzed using both observed case (OC) and last observation carried forward (LOCF) analyses.ResultsOf the 251 patients who entered the OL extension, 51.4% completed 6 months, 36.7% completed 12 months, and 26.7% completed 22 months of OL treatment. Treatment with lurasidone was associated with a mean change from DB baseline, in weight of +0.4 kg at Month 12 (n=99), and +0.8 kg at Month 24 (n=67; OC analyses). Median change from DB baseline to Month 12 and Month 24, respectively, was -1.0 and -9.0 mg/dL for total cholesterol; 0.0 and -1.0 mg/dL for LDL; +1.0 and -11.0 mg/dL for triglycerides; and 0.0 and +0.1/% for HbA1c (OC analyses). The mean PANSS total score was 96.5 at DB baseline and 69.5 at OL baseline. The mean change from DB baseline in the PANSS total score at Month 24 was -43.6 (OC) and -28.4 (LOCF). Thirty-seven patients (14.7%) discontinued due to an adverse event (AE) during OL treatment. Three AEs occurred in ≥10% of patients: schizophrenia (12.4%), akathisia (10.8%), and somnolence (10.8%); and 19.2% reported at least one movement disorder–related AE. Discontinuations due to AEs occurred in 14.8% of patients.ConclusionsIn this 22-month, open-label extension study, treatment with lurasidone was associated with minimal effects on weight, glucose, lipids, and prolactin. Patients demonstrated sustained improvement in the PANSS total score for up to 24 months of lurasidone treatment.

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Long-term safety and efficacy of sarilumab over 5 years in patients with rheumatoid arthritis refractory to TNF inhibitors

Rheumatology ◽

10.1093/rheumatology/keab355 ◽

2021 ◽

Author(s):

Roy Fleischmann ◽

Mark C Genovese ◽

Karina Maslova ◽

Henry Leher ◽

Amy Praestgaard ◽

...

Keyword(s):

Controlled Trial ◽

Tnf Inhibitors ◽

Open Label ◽

Double Blind ◽

Safety And Efficacy ◽

Serious Infection ◽

Open Label Extension ◽

Post Marketing ◽

Grade 3

Abstract Objective To evaluate long-term safety and efficacy of sarilumab over 5 years in patients with RA refractory to TNF inhibitors (TNFi). Methods Patients in the 24-week randomized controlled trial (RCT) TARGET (NCT01709578) whoreceived double-blind placebo or sarilumab 150 or 200 mg every 2 weeks (q2w), plus conventionalsynthetic DMARDs (csDMARDs), were eligible to receive open-label sarilumab 200 mg q2w pluscsDMARDs in the open-label extension (OLE), EXTEND (NCT01146652). OLE dose reduction to 150 mg q2w was permitted per investigators’ judgement or protocol-mandated safety concerns. Safety and efficacy were assessed through treatment-emergent adverse events (AEs), laboratoryabnormalities and clinical disease activity scores. All statistics are descriptive. Results Of 546 patients, 454 (83%) were treated with sarilumab in the OLE. Cumulative observation period was 1654.8 patient-years (PY; n = 521); 268 patients (51%) had ≥4 years’ exposure. Incidencerates per 100 PY of AEs, AEs leading to discontinuation, infection and serious infection were 160.4, 8.1, 57.8 and 3.9, respectively. Neutropenia was the most common AE (15.3 per 100 PY). Absoluteneutrophil count <1000 cells/mm3 (Grade 3/4 neutropenia) was observed in 74 patients (14.2%) and normalized on treatment in 48. Clinical efficacy was sustained through 5 years’ follow-up. Efficacy was similar for patients with 1 and >1 TNFi failure, and between patients who either remained on 200mg or reduced to 150 mg. Conclusion In patients with RA refractory to TNFi, sarilumab’s long-term term safety profile was consistent with previous clinical studies and post-marketing reports. Efficacy was sustained over 5years.

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