A Multicentre, Multinational, Open-Label, 52-Week Extension Study of Gemigliptin (LC15-0444) Monotherapy in Patients with Type 2 Diabetes Mellitus.
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SUBMITTER: Yang SJ
PROVIDER: S-EPMC8369212 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks. METHODS:This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4?g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0?g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale. RESULTS:At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95%?CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period. CONCLUSIONS:Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov (NCT01824251).
| S-EPMC5629934 | biostudies-literature
Project description:IntroductionCentral neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson's disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI.MethodsThis 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5-10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ).ResultsOf the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were -2.3 ± 21.13 mm (CNePSCI), -17.0 ± 24.99 mm (CPSP), and -17.1 ± 35.32 mm (CNePPD).ConclusionMirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study.Trial registrationClinicalTrials.gov identifier, NCT03901352.
| S-EPMC10290008 | biostudies-literature
Project description:During PREVENT (a phase 3, randomized, double-blind, placebo-controlled, time-to-event study) and its open-label extension (interim analysis), 33 adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) received eculizumab monotherapy for a median of 2.8 years (range, 14 weeks-5.2 years). At 192 weeks (~4 years), 96% of these patients were free from adjudicated relapses (Kaplan-Meier analysis; 95% confidence interval, 75.7-99.4). During PREVENT, 95% (20/21) of patients receiving eculizumab monotherapy had no disability worsening. Eculizumab monotherapy provides effective long-term relapse prevention, relieving the chronic immunosuppression burden in patients with AQP4-IgG + NMOSD. ClinicalTrials.gov; PREVENT: NCT01892345; open-label extension: NCT02003144.
| S-EPMC8894682 | biostudies-literature
Project description:Patients with major depressive disorder often experience relapse after responding to treatment; therefore, maintenance therapy with antidepressants is recommended for maintaining response or remission. This multicenter, open-label, flexible-dose, 52-week extension study evaluated the long-term safety, tolerability, and maintenance of efficacy in study participants who had completed one of two randomized, double-blind, placebo-controlled, 8-week dose-ranging vortioxetine trials in study participants with major depressive disorder. At the open-label baseline, all study participants were switched to vortioxetine 5 mg/day for the first week, with subsequent dose adjustments from 2.5 to 10 mg/day on the basis of response and tolerability. Treatment with vortioxetine for 52 weeks was well tolerated, with no new safety signals identified. Among the 834 evaluable study participants, treatment-emergent adverse events were reported in 70.6%, with the most common in the combined (all doses) population of nausea (15.2%), headache (12.4%), nasopharyngitis (9.8%), diarrhea (7.2%), and dizziness (6.8%). The rate of adverse events related to sexual dysfunction was low and weight gain was minimal. Laboratory values, vital signs, ECGs, physical examinations, and Columbia-Suicide Severity Rating Scale results showed no trends of clinical concern. The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set.
| S-EPMC4235387 | biostudies-literature
Project description:Background/purposePreclinical vascular inflammation models have demonstrated effective suppression of arterial wall lesional T cells through inhibition of Janus kinase 3 and JAK1. However, JAK inhibition in patients with giant cell arteritis (GCA) has not been prospectively investigated.MethodsWe performed a prospective, open-label, pilot study of baricitinib (4 mg/day) with a tiered glucocorticoid (GC) entry and accelerated taper in patients with relapsing GCA.Results15 patients were enrolled (11, 73% female) with a mean age at entry of 72.4 (SD 7.2) years, median duration of GCA of 9 (IQR 7-21) months and median of 1 (1-2) prior relapse. Four (27%) patients entered the study on prednisone 30 mg/day, 6 (40%) at 20 mg/day and 5 (33%) at 10 mg/day. Fourteen patients completed 52 weeks of baricitinib. At week 52, 14/15 (93%) patients had ≥1 adverse event (AE) with the most frequent events, including infection not requiring antibiotics (n=8), infection requiring antibiotics (n=5), nausea (n=6), leg swelling (n=2), fatigue (n=2) and diarrhoea (n=1). One subject required baricitinib discontinuation due to AE. One serious adverse event was recorded. Only 1 of 14 (7%) patients relapsed during the study. The remaining 13 patients achieved steroid discontinuation and remained in disease remission during the 52-week study duration.ConclusionIn this proof-of-concept study, baricitinib at 4 mg/day was well tolerated and discontinuation of GC was allowed in most patients with relapsing GCA. Larger randomised clinical trials are needed to determine the utility of JAK inhibition in GCA.Trial registration numberNCT03026504.
| S-EPMC9592156 | biostudies-literature
Project description:IntroductionThe aim of the present study was to assess the long-term (52-week) efficacy and safety of ipragliflozin in insulin-treated Japanese patients with type 1 diabetes mellitus and inadequate glycemic control.Materials and methodsIn this 28-week, open-label extension of a multicenter, randomized, placebo-controlled, 24-week phase III study, ipragliflozin recipients continued treatment (50 mg, once daily), and placebo recipients were switched to once-daily 50 mg ipragliflozin at the start of the extension period. The ipragliflozin dose could be increased to 100 mg if warranted. The primary end-point was change in glycated hemoglobin; secondary end-points were change in insulin dose and bodyweight. Safety outcomes were monitored as treatment-emergent adverse events.ResultsA total of 53 (placebo switched to ipragliflozin) and 108 (ipragliflozin) patients completed the open-label extension (treatment period 2), with 24 and 44 patients, respectively, receiving dose increases. From baseline to end of treatment, the overall mean change (standard deviation [SD]) in glycated hemoglobin was -0.33% (0.72; -3.7 mmol/mol [7.9]), with changes in basal, bolus and total insulin doses of -3.76 IU (SD 3.85 IU), -2.51 IU (SD 7.08 IU) and -6.27 IU (SD 8.16 IU), respectively. No serious drug-related treatment-emergent adverse events or deaths were reported. Treatment-emergent adverse events leading to study discontinuation occurred in zero and three (2.6%) patients in the placebo switched to ipragliflozin and ipragliflozin groups, respectively; all were considered drug-related. There were no cases of severe hypoglycemia or diabetic ketoacidosis, and no safety concerns related to dose increase.ConclusionsThe efficacy and safety of 50 mg, once-daily ipragliflozin in insulin-treated type 1 diabetes mellitus patients were confirmed in this long-term, open-label extension study. No safety concerns were attributed to a dose increase to 100 mg.
| S-EPMC7232286 | biostudies-literature
Project description:AimTo evaluate the safety and efficacy of imeglimin for 52 weeks as monotherapy or combination therapy with existing antidiabetic agents in Japanese patients with type 2 diabetes.Materials and methodsTIMES 2 was a phase 3, pivotal, open-label trial including patients with type 2 diabetes inadequately controlled despite diet/exercise or despite treatment with a single agent from one of several available classes of antidiabetic drugs along with diet/exercise. All patients received imeglimin 1000 mg twice-daily orally for 52 weeks as monotherapy or combination therapy. The primary endpoint was safety (adverse events, laboratory results, ECG). The secondary endpoints were changes from baseline in HbA1c and fasting plasma glucose at week 52.ResultsA total of 714 patients received the following treatments: imeglimin monotherapy (n = 134), combination with an α-glucosidase inhibitor (n = 64), biguanide (n = 64), dipeptidyl peptidase-4 inhibitor (DPP4-I; n = 63), glinide (n = 64), glucagon-like peptide-1 receptor agonist (GLP1-RA; n = 70), sodium-glucose co-transporter-2 inhibitor (n = 63), sulphonylurea (n = 127), or thiazolidinedione (n = 65). The percentage of patients experiencing at least one treatment emergent adverse event (TEAE) was 75.5%. Most of these events were mild or moderate in intensity. Serious TEAEs, none of them related to the study drug, occurred in 5.6% of all patients. No clinically significant changes in ECG, vital signs, physical examination, or laboratory tests were noted in any groups. At week 52, HbA1c decreased by 0.46% with imeglimin monotherapy, by 0.56%-0.92% with imeglimin as oral combination therapy, and by 0.12% with injectable GLP1-RA combination therapy. The greatest net HbA1c reduction (0.92%) occurred in patients receiving a DPP4-I in combination with imeglimin.ConclusionsImeglimin provides well-tolerated, long-term safety and efficacy in both monotherapy and oral combination therapy in Japanese patients with type 2 diabetes.
| S-EPMC9305103 | biostudies-literature
Project description:Vortioxetine is approved for the treatment of adults with major depressive disorder. This open-label extension (OLE) study evaluated the safety and tolerability of vortioxetine in the long-term treatment of major depressive disorder patients, as well as evaluated its effectiveness using measures of depression, anxiety, and overall functioning. This was a 52-week, flexible-dose, OLE study in patients who completed one of three randomized, double-blind, placebo-controlled, 8-week vortioxetine trials. All patients were switched to 10 mg/day vortioxetine for week 1, then adjusted between 15 and 20 mg for the remainder of the study, but not downtitrated below 15 mg. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), vital signs, laboratory values, physical examination, and the Columbia-Suicide Severity Rating Scale. Efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Hamilton Anxiety Scale, the Clinical Global Impression Scale-Severity of Illness, and the Sheehan Disability Scale. Of the 1075 patients enrolled, 1073 received at least one dose of vortioxetine and 538 (50.0%) completed the study. A total of 537 patients withdrew early, with 115 (10.7% of the original study population) withdrawing because of TEAEs. Long-term treatment with vortioxetine was well tolerated; the most common TEAEs (≥10%) were nausea and headache. Laboratory values, vital signs, and physical examinations revealed no trends of clinical concern. The mean Montgomery-Åsberg Depression Rating Scale total score was 19.9 at the start of the extension study and 9.0 after 52 weeks of treatment (observed cases). Similar improvements were observed with the Hamilton Anxiety Scale (Δ-4.2), the Clinical Global Impression Scale-Severity of Illness (Δ-1.2), and the Sheehan Disability Scale (Δ-4.7) total scores after 52 weeks of treatment (observed case). In this 52-week, flexible-dose OLE study, 15 and 20 mg vortioxetine were safe and well tolerated. After entry into this study, patients continued to show improvement in depression and anxiety symptoms, as well as overall functioning, throughout the treatment period.
| S-EPMC4525811 | biostudies-literature
Project description:BACKGROUND:The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. METHODS:This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. RESULTS:Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (<?10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. CONCLUSION:AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.
| S-EPMC6162003 | biostudies-literature
Project description:Aims/introductionTrelagliptin is a novel once-weekly oral dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus that was first approved in Japan. We evaluated long-term safety and efficacy of trelagliptin in Japanese patients with type 2 diabetes mellitus.Materials and methodsThis was a phase 3, multicenter, open-label study to evaluate long-term safety and efficacy of trelagliptin. Patients with type 2 diabetes mellitus inadequately controlled despite diet/exercise or treatment with one of the existing oral antidiabetic drugs along with diet/exercise received trelagliptin 100 mg orally once weekly for 52 weeks as monotherapy or combination therapies. The primary end-points were the safety variables, and the secondary end-points were glycosylated hemoglobin and fasting plasma glucose.ResultsA total of 680 patients received the following antidiabetic therapies: trelagliptin monotherapy (n = 248), combination with a sulfonylurea (n = 158), a glinide (n = 67), an α-glucosidase inhibitor (n = 65), a biguanide (n = 70), or a thiazolidinedione (n = 72). During the study, 79.8% of the patients experienced at least one adverse event for monotherapy, 87.3% for combination with a sulfonylurea, 77.6% for a glinide, 81.5% for an α-glucosidase inhibitor, 64.3% for a biguanide, and 84.7% for a thiazolidinedione, respectively. Most of the adverse events were mild or moderate. The change in glycosylated hemoglobin from baseline at the end of the treatment period was -0.74 to -0.25% for each therapy.ConclusionsOnce-weekly oral trelagliptin provides well-tolerated long-term safety and efficacy in both monotherapy and combination therapies in Japanese patients with type 2 diabetes mellitus.
| S-EPMC5009134 | biostudies-literature