The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Curt D. Wolfgang - One of the best experts on this subject based on the ideXlab platform.
-
a randomized trial of Iloperidone for prevention of relapse in schizophrenia the reprieve study
CNS Drugs, 2016Co-Authors: Peter J Weiden, Curt D. Wolfgang, Raymond Manning, Michael J Ryan, Linda Mancione, Guangyang Han, Saeed Ahmed, Mallery G MayoAbstract:Background The purpose of this study was to evaluate the safety and effectiveness of Iloperidone for the prevention of relapse in schizophrenia.
-
four week double blind placebo and ziprasidone controlled trial of Iloperidone in patients with acute exacerbations of schizophrenia
Journal of Clinical Psychopharmacology, 2008Co-Authors: Andrew J. Cutler, Amir H Kalali, Peter J Weiden, Jennifer Hamilton, Curt D. WolfgangAbstract:Iloperidone is a mixed D2/5-HT2 antagonist in development for treatment of schizophrenia. This trial aimed to evaluate the efficacy and safety of a fixed dose of Iloperidone in patients with acute exacerbations of schizophrenia. This randomized, placebo-controlled, multicenter study comprised a 1-week titration period and a 3-week double-blind maintenance period. Eligible patients (n = 593) were randomized to Iloperidone 24 mg/d, ziprasidone 160 mg/d as an active control, or placebo. Primary efficacy variable was change from baseline in the Positive and Negative Syndrome Scale Total (PANSS-T) score, using a mixed-effects model repeated measures analysis. Iloperidone demonstrated significant reduction versus placebo on the PANSS-T score (P< 0.01). Significant improvement versus placebo was also demonstrated with ziprasidone (P < 0.05). Compared with ziprasidone, Iloperidone was associated with lower rates of many adverse events (AEs) that are particularly troublesome with antipsychotics, including sedation, somnolence, extrapyramidal symptoms, akathisia, agitation, and restlessness; Iloperidone was associated with higher rates of weight gain, tachycardia, orthostatic hypotension, dizziness, and nasal congestion as reported as an AE. Most AEs were mild to moderate. A similar amount of QT prolongation was observed with both active treatments, although no patient had a treatment-emergent postbaseline corrected QT interval of 500 msec or greater. The incidence of clinically relevant changes in laboratory parameters was comparable between Iloperidone and ziprasidone. Iloperidone was associated with a low incidence of extrapyramidal symptoms. Overall, there was improvement in akathisia with Iloperidone treatment. Iloperidone treatment was effective, safe, and well tolerated in patients with acute exacerbation of schizophrenia.
-
safety profile of Iloperidone a pooled analysis of 6 week acute phase pivotal trials
Journal of Clinical Psychopharmacology, 2008Co-Authors: Peter J Weiden, M H Polymeropoulos, Andrew J. Cutler, Curt D. WolfgangAbstract:Iloperidone, a mixed D2/5-HT2 antagonist, is currently in clinical development for the treatment of schizophrenia. This article assesses the short-term safety of Iloperidone using a pooled analysis of 3 phase 2, short-term acute schizophrenia studies conducted between 1998 and 2002 (N = 1943). Patients exposed to 3 dose ranges of Iloperidone, another antipsychotic, or placebo were compared on rates of serious adverse events (SAEs), adverse events (AEs), extrapyramidal symptoms, akathisia, prolactin, weight and metabolic parameters, QTc, and other standard safety parameters. The most common treatment-related AEs observed with Iloperidone were dizziness, headache, dry mouth, nausea, and insomnia. Discontinuation due to AEs was 4.8% for Iloperidone, 7.6% for haloperidol, 6.2% for risperidone, and 4.8% for placebo. Iloperidone groups showed better overall performance on the Extrapyramidal Symptom Rating Scale and Barnes Akathisia Scale than risperidone or haloperidol groups. Patients taking Iloperidone experienced a mild weight increase (range, 1.5-2.1 kg) similar to that of risperidone (1.5 kg), whereas those on haloperidol and placebo showed mean weight loss (-0.1 kg and -0.3 kg, respectively). QTc interval significantly increased across all Iloperidone groups (least squares mean change from baseline to end point, 2.9-9.1 msec) and for haloperidol (5.0 msec). No significant QTc changes occurred in the risperidone or placebo groups. Iloperidone was associated with no change from baseline in total cholesterol, mild elevation in serum glucose, and slight decrease in triglycerides. Prolactin levels decreased with Iloperidone and increased significantly with risperidone and haloperidol. These short-term trials suggest that Iloperidone has a reassuring safety profile in many of the areas that are of potential concern, including relatively low dropout rates because of AEs, low extrapyramidal symptoms, akathisia, and prolactin elevation, and a modest short-term effect on weight gain.
-
long term efficacy and safety of Iloperidone results from 3 clinical trials for the treatment of schizophrenia
Journal of Clinical Psychopharmacology, 2008Co-Authors: John M Kane, John Lauriello, Eugene M Laska, Michael Di Marino, Curt D. WolfgangAbstract:This research compared the long-term efficacy and safety of Iloperidone with those of haloperidol in individuals with schizophrenia. Data were pooled from 3 prospective multicenter studies, each with 6-week stabilization followed by 46-week double-blind maintenance phases. Patients were randomized to Iloperidone 4 to 16 mg/d or haloperidol 5 to 20 mg/d. Patients included in this analysis completed the initial 6-week phase with at least 20% reduction in Positive and Negative Syndrome Scale (PANSS) total score at weeks 4 and 6, had 7-item Clinical Global Impressions of Change (CGI-C) scores less than 4, received 1 or more doses of long-term phase medication, and had 1 or more efficacy/safety assessments during the long-term phase. The primary efficacy variable was time to relapse, defined as a 25% or more increase in PANSS total score, including at least a 10-point change; discontinuation because of lack of efficacy; aggravated psychosis with hospitalization; or 2-point increase in the 7-item CGI-C after week 6. Of 1644 patients randomized and 1326 completing the 6-week phase, 473 (Iloperidone, n = 359; haloperidol, n = 114) were included in the long-term efficacy analysis, and 489 (Iloperidone, n = 371; haloperidol, n = 118) in the safety analysis. Iloperidone was equivalent to haloperidol in time to relapse. The most common adverse events were insomnia (18.1%), anxiety (10.8%), and schizophrenia aggravated (8.9%) with Iloperidone, and insomnia (16.9%), akathisia (14.4%), tremor (12.7%), and muscle rigidity (12.7%) with haloperidol. The Extrapyramidal Symptoms Rating Scale scores improved with Iloperidone and worsened with haloperidol. Metabolic changes were minimal for both groups. Mean changes in Fridericia's QT interval correction were 10.3 msec (Iloperidone) and 9.4 msec (haloperidol) at end point. Iloperidone demonstrated long-term efficacy equivalent to haloperidol and a favorable long-term safety profile, potentially making this agent a suitable option as maintenance therapy for schizophrenia.
-
efficacy of Iloperidone in the treatment of schizophrenia initial phase 3 studies
Journal of Clinical Psychopharmacology, 2008Co-Authors: Steven G Potkin, Robert E Litman, Torres Rosarelis, Curt D. WolfgangAbstract:Iloperidone is an atypical antipsychotic in development for the treatment of schizophrenia. This report examines efficacy results from three 6-week, randomized, double-blind, placebo- and active comparator-controlled studies in patients with schizophrenia or schizoaffective disorder. Multiple doses of Iloperidone were studied. Active comparators (haloperidol 15 mg/d, or risperidone 4-8 mg/d) were included to confirm trial validity. The primary protocol-defined efficacy variable in Study 1 was change from baseline to end point in Positive and Negative Syndrome Scale total scores; in Studies 2 and 3, it was change in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale scores. Results were assessed through analysis of covariance using last observation carried forward in the intent-to-treat population. In total, 1943 patients were randomized. At least 1 Iloperidone dosing group in each study demonstrated significantly better efficacy than placebo (Study 1, Iloperidone 12 mg/d [P = 0.047]; Study 2, 4-8 mg/d [P = 0.012] and 10-16 mg/d [P = 0.001]; and Study 3, 20-24 mg/d [P = 0.010]). Active controls were also significantly more effective than placebo in each trial, thus validating the trials. Additional analysis in patients who received active treatment for at least 2 weeks indicated comparable efficacy score reductions at 6 weeks for patients receiving Iloperidone 20 to 24 mg/d versus those receiving haloperidol or risperidone. Risk for motor-related adverse events (eg, akathisia and extrapyramidal symptoms) was lower with Iloperidone than with risperidone and haloperidol and was generally similar to placebo. These trials indicate that Iloperidone is effective for the treatment of schizophrenia.
Leslie Citrome - One of the best experts on this subject based on the ideXlab platform.
-
a trial evaluating gradual or immediate switch strategies from risperidone olanzapine or aripiprazole to Iloperidone in patients with schizophrenia
Schizophrenia Research, 2014Co-Authors: Peter J Weiden, Leslie Citrome, Xiangyi Meng, Gus Alva, Matthew Brams, Ira D Glick, Richard Jackson, Greg Mattingly, Farid Kianifard, Linda PestreichAbstract:In a 12-week randomized open-label trial, adults diagnosed with schizophrenia experiencing inadequate efficacy and/or poor tolerability on risperidone, olanzapine, or aripiprazole were randomized to switch to Iloperidone either gradually (ie, down-titration of current therapy over the first 2weeks [to 50% on Day 1, 25% by Week 1, 0% by Week 2]) or immediately. All patients were titrated on Iloperidone to 6mg BID by Day 4, then flexibly dosing between 6 and 12mg BID, as needed. The primary variable was the Integrated Clinical Global Impression of Change (I-CGI-C) and the primary analysis time point was Week 12. A total of 500 patients were randomized and received Iloperidone (gradual switch, 240; immediate switch, 260), with 175, 155, and 170 patients switched from risperidone, olanzapine, and aripiprazole, respectively. I-CGI-C Results confirmed improved outcomes at Week 12, with scores that were similar between the gradual- and immediate-switch groups, respectively, for risperidone, 2.82 and 2.67 (95% CI: -0.229, 0.511); olanzapine, 2.87 and 3.03 (95% CI: -0.548, 0.235); and aripiprazole, 2.79 and 2.81 (95% CI: -0.405, 0.368). Incidence of adverse events (AEs) was similar in both switch groups, with the most frequently reported (≥10%) being dizziness, dry mouth, somnolence, and weight increase. In conclusion, switching to Iloperidone by either a gradual or an immediate method did not reveal any clinically significant differences in ratings of overall efficacy and safety/tolerability outcomes, based on the I-CGI-C at 12weeks. Similar overall safety/AE profiles were observed regardless of the specific agent from which patients were switched.
-
efficacy of Iloperidone in the short term treatment of schizophrenia a post hoc analysis of pooled patient data from four phase iii placebo and active controlled trials
Human Psychopharmacology-clinical and Experimental, 2012Co-Authors: Leslie Citrome, Marla Hochfeld, Xiangyi Meng, S StahlAbstract:Objectives The efficacy and tolerability characteristics of an antipsychotic are difficult to determine from a single registration study. We thus conducted an analysis that assessed key efficacy and tolerability outcomes post hoc from four pooled short-term (4–6 weeks) phase III studies that evaluated Iloperidone versus placebo in patients with schizophrenia or schizoaffective disorder. Methods Patient-level data were pooled from four prospective, randomized, double-blind, placebo-controlled and active-controlled, multicenter trials of Iloperidone in patients with schizophrenia or schizoaffective disorder aged 18–65 years. Iloperidone 4–8, 10–16, and 20–24 mg/day (all dosed twice daily) were compared with placebo. Active controls used for assay sensitivity included risperidone 4–8 mg/day, haloperidol 15 mg/day, and ziprasidone 160 mg/day. Outcomes of interest were change from baseline to endpoint in the Brief Psychiatric Rating Scale (derived) (BPRSd), Positive and Negative Syndrome Scale (PANSS)-total (PANSS-T) score, and PANSS-positive (PANSS-P) and PANSS-negative (PANSS-N) subscale scores. An analysis of covariance (with treatment and study as factors, baseline as a covariate) was performed to compare changes between the Iloperidone treatment groups versus placebo, on the basis of a last-observation-carried-forward approach for the intent-to-treat (ITT) populations. Tolerability outcomes were obtained from spontaneously reported adverse events (AEs), and number needed to harm was calculated for each antipsychotic versus placebo for the total population. Results The ITT population included both schizoaffective and schizophrenia patients (N = 2401): n = 370, n = 494, and n = 424 for Iloperidone 4–8, 10–16, and 20–24 mg/day, respectively; n = 294 for risperidone; n = 114 for haloperidol; n = 144 for ziprasidone; and n = 561 for placebo. Treatment with Iloperidone 10–16 mg/day or 20–24 mg/day was associated with significantly improved BPRSd, PANSS-T, PANSS-P, and PANSS-N scores versus treatment with placebo. When only patients with schizophrenia were included (n = 1941), the pattern of results was essentially unchanged. The active controls confirmed assay sensitivity. Across all Iloperidone dose groups, the incidences of extrapyramidal disorders and akathisia were similar to those observed with placebo. AEs for which the frequency was greater for Iloperidone than placebo and for which the 95% confidence interval for number needed to harm did not contain infinity were dizziness, dry mouth, somnolence, nasal congestion, fatigue, sedation, and tachycardia; in general, for these AEs, frequency was higher with higher doses, resulting in a lower number needed to harm. Conclusions Consistent with product labeling, Iloperidone 10–16 mg/day or 20–24 mg/day demonstrated significant improvement over placebo on BPRSd and PANSS-T scores, as well as on PANSS-P and PANSS-N subscale scores over 6 weeks of treatment in patients with schizophrenia and in the ITT population, which includes patients with schizoaffective disorder. Iloperidone did not differ from placebo in terms of extrapyramidal disorders and akathisia. Copyright © 2011 John Wiley & Sons, Ltd.
-
Iloperidone a clinical overview
The Journal of Clinical Psychiatry, 2011Co-Authors: Leslie CitromeAbstract:Iloperidone is a new second-generation (atypical) antipsychotic medication approved for the treatment of schizophrenia in adults. The target dose of 6 mg bid can be achieved in 4 days, with titration recommended to minimize postural hypotension. The maximum recommended dose is 12 mg bid. The tolerability profile of Iloperidone is noteworthy in terms of modest weight gain, no medically important changes in lipid and glucose levels, little in the way of prolactin elevation, and absence of extrapyramidal side effects, including akathisia. However, Iloperidone can prolong the QTc interval on electrocardiogram. Iloperidone may be best suited for patients who are sensitive to akathisia or who are unable to tolerate the sedation and weight gain that can occur more frequently with other antipsychotics.
-
efficacy of Iloperidone in schizophrenia a panss five factor analysis
Schizophrenia Research, 2011Co-Authors: Leslie Citrome, Xiangyi Meng, Marla HochfeldAbstract:Abstract Background The Positive and Negative Syndrome Scale (PANSS) total score is widely used to assess antipsychotic efficacy, however schizophrenia is a multi-dimensional disorder. We conducted a 5-factor analysis for evaluating the efficacy of Iloperidone vs. placebo across these different domains in the treatment of schizophrenia. Method The 5-factor model was determined from pooled data from 7 clinical trials (4 placebo- and active-controlled and 3 non-inferiority active-comparator trials of Iloperidone) in schizophrenia (N = 3580).Five factors were derived (excitement/hostility [P4,P7,G8,G14], depression/anxiety [G1,G2,G3,G4,G6], cognition [P2,N5,N7,G5,G10,G11,G12,G13,G15], positive [P1,P3,P5,P6,G9], and negative [N1,N2,N3,N4,N6,G7,G16]) from a factor analysis on the covariance matrix of 30 baseline PANSS items using a varimax rotation; factors retained had eigenvalues of ≥ 0.5. These newly derived 5 factors differ only slightly from other 5-factor analyses published by others using different datasets. The analysis of covariance model was then applied to assess these efficacy outcomes from the 4–6 week double-blind placebo and active controlled clinical trials of Iloperidone. Results Based on the placebo-controlled trials, Iloperidone improvements from baseline (least squared mean change ± standard error) were as follows: excitement/hostility, 0.4 ± 0.21 for 10–16 mg, 0.6 ± 0.43 for 20–24 mg vs. −1.0 ± 0.23 for placebo; P P P P P Conclusions Iloperidone demonstrated positive treatment effects on these newly derived PANSS factors. The 10–16 mg and 20–24 mg dose groups had similar efficacy on the PANSS factors, with the exception of the depression/anxiety and negative factors, on which the 10–16 mg dose group showed statistical separation from placebo and the 20–24 mg dose group did not. At 6 weeks, the lack of separation from placebo for the higher dose group may have been due to the much smaller sample size in that group.
-
Iloperidone asenapine and lurasidone a brief overview of 3 new second generation antipsychotics
Postgraduate Medicine, 2011Co-Authors: Leslie CitromeAbstract:Three new second-generation antipsychotics were approved by the US Food and Drug Administration in 2009 and 2010: Iloperidone, asenapine, and lurasidone. All 3 agents are approved for the treatment of acute schizophrenia in adults, and asenapine is also approved for the maintenance treatment of schizophrenia and as a monotherapy or as an adjunct to lithium or valproate for the treatment of bipolar manic or mixed episodes. The expectation is that these new agents will be less problematic regarding treatment-emergent weight gain and metabolic disturbances, which unfortunately can occur with several other second-generation antipsychotics. Asenapine is a sublingual preparation, in contrast to Iloperidone and lurasidone, which are swallowed. Iloperidone and asenapine are dosed twice daily, in contrast to lurasidone, which is dosed once daily with food. Both asenapine and lurasidone can be initiated at a dose that is possibly therapeutic, but Iloperidone requires 4 days of titration to reach its recommended target dose range. Although both asenapine and lurasidone can be associated with dose-related treatment-emergent akathisia, Iloperidone is essentially free of extrapyramidal adverse effects or akathisia throughout its recommended dose range. Sedation and/or somnolence have been reported with each medication. They are the most common adverse events associated with asenapine treatment, and are clearly dose-related for lurasidone. In contrast, no therapeutic dose response for Iloperidone, asenapine, or lurasidone is clearly evident from short-term clinical trials. Longer-term and naturalistic studies will be helpful in evaluating these agents and their role in the psychiatric armamentarium.
C Lavedan - One of the best experts on this subject based on the ideXlab platform.
-
absence of weight gain association with the htr2c 759c t polymorphism in patients with schizophrenia treated with Iloperidone
Psychiatry Research-neuroimaging, 2010Co-Authors: Andrew Thompson, C Lavedan, Simona VolpiAbstract:Weight gain is a common side effect of antipsychotics, contributing to poor treatment adherence, and previously linked to the -759C/T polymorphism near the serotonin receptor 2C gene. The effect of this polymorphism was analyzed in schizophrenia patients treated with Iloperidone for up to 7 months. No association was detected with the modest weight changes observed in these patients.
-
Whole genome association study identifies polymorphisms associated with QT prolongation during Iloperidone treatment of schizophrenia
Molecular Psychiatry, 2009Co-Authors: S Volpi, C Heaton, K Mack, J B Hamilton, R Lannan, C D Wolfgang, L Licamele, M H Polymeropoulos, C LavedanAbstract:Administration of certain drugs (for example, antiarrhythmics, antihistamines, antibiotics, antipsychotics) may occasionally affect myocardial repolarization and cause prolongation of the QT interval. We performed a whole genome association study of drug-induced QT prolongation after 14 days of treatment in a phase 3 clinical trial evaluating the efficacy, safety and tolerability of a novel atypical antipsychotic, Iloperidone, in patients with schizophrenia. We identified DNA polymorphisms associated with QT prolongation in six loci, including the CERKL and SLCO3A1 genes. Each single nucleotide polymorphism (SNP) defined two genotype groups associated with a low mean QT change (ranging from −0.69 to 5.67 ms depending on the SNP) or a higher mean QT prolongation (ranging from 14.16 to 17.81 ms). The CERKL protein is thought to be part of the ceramide pathway, which regulates currents conducted by various potassium channels, including the hERG channel. It is well established that inhibition of the hERG channel can prolong the QT interval. SLCO3A1 is thought to play a role in the translocation of prostaglandins, which have known cardioprotective properties, including the prevention of torsades de pointes. Our findings also point to genes involved in myocardial infarction ( PALLD ), cardiac structure and function ( BRUNOL4 ) and cardiac development ( NRG3 ). Results of this pharmacogenomic study provide new insight into the clinical response to Iloperidone, developed with the goal of directing therapy to those patients with the optimal benefit/risk ratio.
-
Association of the NPAS3 gene and five other loci with response to the antipsychotic Iloperidone identified in a whole genome association study
Molecular Psychiatry, 2009Co-Authors: C Lavedan, S Volpi, C Heaton, K Mack, R Lannan, C D Wolfgang, L Licamele, J Hamilton, A Thompson, M H PolymeropoulosAbstract:A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, Iloperidone, administered to treat patients with schizophrenia. Genotypes of 407 patients were analyzed for 334 563 single nucleotide polymorphisms (SNPs). SNPs associated with Iloperidone efficacy were identified within the neuronal PAS domain protein 3 gene ( NPAS3 ), close to a translocation breakpoint site previously observed in a family with schizophrenia. Five other loci were identified that include the XK, Kell blood group complex subunit-related family, member 4 gene ( XKR4 ), the tenascin-R gene ( TNR ), the glutamate receptor, inotropic, AMPA 4 gene ( GRIA4 ), the glial cell line-derived neurotrophic factor receptor-alpha2 gene ( GFRA2 ), and the NUDT9P1 pseudogene located in the chromosomal region of the serotonin receptor 7 gene ( HTR7 ). The study of these polymorphisms and genes may lead to a better understanding of the etiology of schizophrenia and of its treatment. These results provide new insight into response to Iloperidone, developed with the ultimate goal of directing therapy to patients with the highest benefit-to-risk ratio.
-
applicability of a genetic signature for enhanced Iloperidone efficacy in the treatment of schizophrenia
The Journal of Clinical Psychiatry, 2009Co-Authors: Simona Volpi, L Licamele, Anil K Malhotra, Steven G Potkin, C LavedanAbstract:OBJECTIVE To demonstrate how several polymorphisms previously associated with the efficacy of the novel antipsychotic Iloperidone could be used together to predict clinical response and provide practical information for individualized treatment. METHOD This inpatient randomized, double-blind, placebo- and ziprasidone-controlled, 28-day study of the efficacy of Iloperidone was conducted from November 2005 to September 2006. Likelihood ratios, predicted probabilities of response, and number needed to treat were calculated for patients with schizophrenia (DSM-IV criteria) using 6 genetic markers of Iloperidone response as measured by change in the Positive and Negative Syndrome Scale-Total (PANSS-T) score. Data analysis was performed on 409 patients of various ethnic origins. RESULTS The 6-marker genotype combinations defined 4 groups of patients with distinct probabilities of response. More than 75% of Iloperidone-treated patients in the group with the optimal genotype combinations showed a 20% or greater improvement, compared with 37% for patients with other genotypes. These patients had a significant response by the first week of treatment, which was earlier than for patients with other genotype combinations. The odds of responding to Iloperidone treatment with at least 20% improvement ranged from 2.4 to 3.6 for patients with 1 of the 6 favorable single-marker genotypes. The odds increased to 9.5 or greater for patients with the most favorable 6-marker combinations. The difference in PANSS-T score improvement observed between the genotype groups was also seen for the positive, negative, and general psychopathology PANSS subscales. The relationship between treatment efficacy and genotype combinations was not observed for patients treated with ziprasidone. CONCLUSION These results illustrate the combined use of genetic markers to predict enhanced response to Iloperidone and support the application of pharmacogenetics to differentiate medication options and improve individualized treatments for schizophrenia. TRIAL REGISTRATION (ClinicalTrials.gov) Identifier: NCT00254202.
-
Effect of a ciliary neurotrophic factor polymorphism on schizophrenia symptom improvement in an Iloperidone clinical trial
Pharmacogenomics, 2008Co-Authors: C Lavedan, M H Polymeropoulos, Simona Volpi, Curt D. WolfgangAbstract:Aims: Presence of the null FS63TER allele of the rs1800169 polymorphism in the gene encoding the ciliary neurotrophic factor (CNTF) may increase the risk of schizophrenia. This study prospectively evaluated the CNTF rs1800169 genotype (G/G vs non-G/G) effects on response to Iloperidone. Patients & Methods: Iloperidone 24 mg/day was evaluated in a study of patients with schizophrenia. Efficacy measurements included Positive and Negative Syndrome Scale total (PANSS-T), Brief Psychiatric Rating Scale (BPRS) and Clinical, Global, Impression (CGI) scores. The step-down primary end point was the difference in PANSS-T scores based on CNTF rs1800169 G/G genotype. Results: This study genotyped 417 patients (279 Iloperidone and 138 placebo) for the rs1800169 polymorphism. Iloperidone significantly improved PANSS-T, PANSS positive subscale (PANSS-P), PANSS negative subscale (PANSS-N), BPRS, Clinical Global Impression of Change (CGI-C) and Clinical Global Impression of Severity (CGI-S) scores versus placebo. G/G vers...
Maria Augusta Raggi - One of the best experts on this subject based on the ideXlab platform.
-
Iloperidone: a new benzisoxazole atypical antipsychotic drug: is it nove enough to impact the crowded atypical antipsychotic market?
'Informa Healthcare', 2008Co-Authors: Lawrence J. Albers, Alessandro Musenga, Maria Augusta RaggiAbstract:Iloperidone (Zomaril\uae) is a new generation atypical antipsychotic agent, acting as a 5-HT2A/D2 antagonist, currently under development by Vanda Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other psychiatric conditions. Chemically Iloperidone is a benzisoxazole, like Risperidone, and shows a multiple receptor binding profile, sharing this feature with the other atypical antipsychotic agents. Administered orally, the drug is highly bound to plasma proteins and extensively metabolised; reduced Iloperidone is the main active metabolite. Several clinical trials were carried out, to check efficacy, safety and side effects. In order to introduce Iloperidone as an agent for the treatment of schizophrenia, a short overview of the disease and of the most important available or under development antipsychotic drugs will be reported as well. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results
-
Iloperidone: a new benzisoxazole atypical antipsychotic drug: is it nove enough to impact the crowded atypical antipsychotic market?
2008Co-Authors: Lawrence J. Albers, Alessandro Musenga, Maria Augusta RaggiAbstract:Iloperidone (Zomaril®) is a new generation atypical antipsychotic agent, acting as a 5-HT2A/D2 antagonist, currently under development by Vanda Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other psychiatric conditions. Chemically Iloperidone is a benzisoxazole, like Risperidone, and shows a multiple receptor binding profile, sharing this feature with the other atypical antipsychotic agents. Administered orally, the drug is highly bound to plasma proteins and extensively metabolised; reduced Iloperidone is the main active metabolite. Several clinical trials were carried out, to check efficacy, safety and side effects. In order to introduce Iloperidone as an agent for the treatment of schizophrenia, a short overview of the disease and of the most important available or under development antipsychotic drugs will be reported as well. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results
-
Iloperidone a new benzisoxazole atypical antipsychotic drug is it novel enough to impact the crowded atypical antipsychotic market
Expert Opinion on Investigational Drugs, 2008Co-Authors: Lawrence J. Albers, Alessandro Musenga, Maria Augusta RaggiAbstract:Iloperidone is a new-generation atypical antipsychotic agent, acting as a serotonin/dopamine (5-HT2A/D2) antagonist, under development by Vanda Pharmaceuticals for the treatment of schizophrenia, b...
-
Iloperidone: a new benzisoxazole atypical antipsychotic drug. Is it novel enough to impact the crowded atypical antipsychotic market?
Expert Opinion on Investigational Drugs, 2007Co-Authors: Lawrence J. Albers, Alessandro Musenga, Maria Augusta RaggiAbstract:Iloperidone is a new-generation atypical antipsychotic agent, acting as a serotonin/dopamine (5-HT(2A)/D(2)) antagonist, under development by Vanda Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other psychiatric conditions. Chemically, Iloperidone is a benzisoxazole, like risperidone, and shows a multiple receptor binding profile, sharing this feature with the other atypical antipsychotic agents. Administered orally, the drug is highly bound to plasma proteins and extensively metabolised. Several clinical trials have been carried out, to check efficacy, safety and side effects. In order to introduce Iloperidone as an agent for the treatment of schizophrenia, a short overview of the disease and of the most important antipsychotic drugs available or under development will be reported. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results.
Xiangyi Meng - One of the best experts on this subject based on the ideXlab platform.
-
a trial evaluating gradual or immediate switch strategies from risperidone olanzapine or aripiprazole to Iloperidone in patients with schizophrenia
Schizophrenia Research, 2014Co-Authors: Peter J Weiden, Leslie Citrome, Xiangyi Meng, Gus Alva, Matthew Brams, Ira D Glick, Richard Jackson, Greg Mattingly, Farid Kianifard, Linda PestreichAbstract:In a 12-week randomized open-label trial, adults diagnosed with schizophrenia experiencing inadequate efficacy and/or poor tolerability on risperidone, olanzapine, or aripiprazole were randomized to switch to Iloperidone either gradually (ie, down-titration of current therapy over the first 2weeks [to 50% on Day 1, 25% by Week 1, 0% by Week 2]) or immediately. All patients were titrated on Iloperidone to 6mg BID by Day 4, then flexibly dosing between 6 and 12mg BID, as needed. The primary variable was the Integrated Clinical Global Impression of Change (I-CGI-C) and the primary analysis time point was Week 12. A total of 500 patients were randomized and received Iloperidone (gradual switch, 240; immediate switch, 260), with 175, 155, and 170 patients switched from risperidone, olanzapine, and aripiprazole, respectively. I-CGI-C Results confirmed improved outcomes at Week 12, with scores that were similar between the gradual- and immediate-switch groups, respectively, for risperidone, 2.82 and 2.67 (95% CI: -0.229, 0.511); olanzapine, 2.87 and 3.03 (95% CI: -0.548, 0.235); and aripiprazole, 2.79 and 2.81 (95% CI: -0.405, 0.368). Incidence of adverse events (AEs) was similar in both switch groups, with the most frequently reported (≥10%) being dizziness, dry mouth, somnolence, and weight increase. In conclusion, switching to Iloperidone by either a gradual or an immediate method did not reveal any clinically significant differences in ratings of overall efficacy and safety/tolerability outcomes, based on the I-CGI-C at 12weeks. Similar overall safety/AE profiles were observed regardless of the specific agent from which patients were switched.
-
a thorough qtc study of 3 doses of Iloperidone including metabolic inhibition via cyp2d6 and or cyp3a4 and a comparison to quetiapine and ziprasidone
Journal of Clinical Psychopharmacology, 2013Co-Authors: Steven G Potkin, Sheldon H Preskorn, Marla Hochfeld, Xiangyi MengAbstract:The potential for Iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rate-corrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-label, multicenter study. QT interval prolongation by medications, including both conventional and atypical antipsychotic drugs, can predispose patients to cardiac arrhythmias and result in sudden death. Adults with schizophrenia or schizoaffective disorder and normal electrocardiograms at baseline (N = 188) were randomized 1:1:1:1:1 to Iloperidone, 8 mg twice daily (BID), 12 mg BID, 24 mg once daily (QD); quetiapine, 375 mg BID; or ziprasidone, 80 mg BID during period 1 (no metabolic inhibitors present). Iloperidone BID produced mean changes in QTc Fridericia correction (QTcF) interval (8.5-9.0 milliseconds [ms]) similar to those produced by ziprasidone (9.6 ms) and higher than those produced by quetiapine (1.3 ms). Iloperidone, 24 mg QD, produced a mean QTcF change of 15.4 ms. Coadministration of metabolic inhibitors with Iloperidone during periods 2 (paroxetine) and 3 (paroxetine and ketoconazole) resulted in greater increases in the QTc interval. Increased QTc was observed in individuals with specific cytochrome P450 2D6 polymorphisms. Up to 10% of patients on Iloperidone experienced QTc intervals of 60 ms or longer in the presence of metabolic inhibition and QD dosing. However, no patients experienced QTc changes of clinical concern (QTc ≥ 500 ms). The most common adverse events with Iloperidone were headache, anxiety, and dyspepsia. The only cardiovascular adverse events with Iloperidone were non-concentration-dependent tachycardia that was mild in most patients and did not lead to further sequelae. Pharmacogenetics and recommendations are discussed.
-
a thorough qtc study of 3 doses of Iloperidone including metabolic inhibition via cyp2d6 and or cyp3a4 and a comparison to quetiapine and ziprasidone
Journal of Clinical Psychopharmacology, 2013Co-Authors: Steven G Potkin, Sheldon H Preskorn, Marla Hochfeld, Xiangyi MengAbstract:AbstractThe potential for Iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rate–corrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-label, multicenter study. QT interval prolongation by medications, including both conventional
-
long term safety and tolerability of Iloperidone results from a 25 week open label extension trial
Cns Spectrums, 2013Co-Authors: Andrew J. Cutler, Amir H Kalali, Greg Mattingly, Jelena Kunovac, Xiangyi MengAbstract:Introduction/ObjectiveLong-term use of the atypical antipsychotic Iloperidone has not been investigated at doses above 16 mg/d. This article describes safety and tolerability results from the 25-week open-label extension of a 4-week placebo- and ziprasidone-controlled clinical trial of Iloperidone.MethodsPatients received a dose of 24 mg/d (given as 12 mg twice daily; mean dose = 21.6 mg) that could be reduced to 12 mg/d (given once daily at bedtime) any time after day 35 at the investigator's discretion.ResultsA total of 72/173 patients (41.6%) completed the open-label extension. Treatment-emergent adverse events (TEAEs), most mild to moderate in severity, included headache (13.9%), weight increase (9.2%), dizziness (6.9%), nausea (6.4%), sedation (6.4%), and insomnia (5.2%). The only notable dose-related TEAEs were increased weight and headache. Levels of serum glucose, lipids, and prolactin were essentially unchanged or decreased during treatment. In general, akathisia and extrapyramidal symptoms (EPS) improved or were unchanged during treatment. There was no signal of worsening of efficacy based on changes from baseline in the Positive and Negative Syndrome Scale-Total.Discussion/ConclusionThis study further supports the long-term safety and tolerability of Iloperidone for the treatment of schizophrenia, including Iloperidone's favorable effect on metabolic laboratory parameters and low propensity to cause akathisia or EPS.
-
efficacy of Iloperidone in the short term treatment of schizophrenia a post hoc analysis of pooled patient data from four phase iii placebo and active controlled trials
Human Psychopharmacology-clinical and Experimental, 2012Co-Authors: Leslie Citrome, Marla Hochfeld, Xiangyi Meng, S StahlAbstract:Objectives The efficacy and tolerability characteristics of an antipsychotic are difficult to determine from a single registration study. We thus conducted an analysis that assessed key efficacy and tolerability outcomes post hoc from four pooled short-term (4–6 weeks) phase III studies that evaluated Iloperidone versus placebo in patients with schizophrenia or schizoaffective disorder. Methods Patient-level data were pooled from four prospective, randomized, double-blind, placebo-controlled and active-controlled, multicenter trials of Iloperidone in patients with schizophrenia or schizoaffective disorder aged 18–65 years. Iloperidone 4–8, 10–16, and 20–24 mg/day (all dosed twice daily) were compared with placebo. Active controls used for assay sensitivity included risperidone 4–8 mg/day, haloperidol 15 mg/day, and ziprasidone 160 mg/day. Outcomes of interest were change from baseline to endpoint in the Brief Psychiatric Rating Scale (derived) (BPRSd), Positive and Negative Syndrome Scale (PANSS)-total (PANSS-T) score, and PANSS-positive (PANSS-P) and PANSS-negative (PANSS-N) subscale scores. An analysis of covariance (with treatment and study as factors, baseline as a covariate) was performed to compare changes between the Iloperidone treatment groups versus placebo, on the basis of a last-observation-carried-forward approach for the intent-to-treat (ITT) populations. Tolerability outcomes were obtained from spontaneously reported adverse events (AEs), and number needed to harm was calculated for each antipsychotic versus placebo for the total population. Results The ITT population included both schizoaffective and schizophrenia patients (N = 2401): n = 370, n = 494, and n = 424 for Iloperidone 4–8, 10–16, and 20–24 mg/day, respectively; n = 294 for risperidone; n = 114 for haloperidol; n = 144 for ziprasidone; and n = 561 for placebo. Treatment with Iloperidone 10–16 mg/day or 20–24 mg/day was associated with significantly improved BPRSd, PANSS-T, PANSS-P, and PANSS-N scores versus treatment with placebo. When only patients with schizophrenia were included (n = 1941), the pattern of results was essentially unchanged. The active controls confirmed assay sensitivity. Across all Iloperidone dose groups, the incidences of extrapyramidal disorders and akathisia were similar to those observed with placebo. AEs for which the frequency was greater for Iloperidone than placebo and for which the 95% confidence interval for number needed to harm did not contain infinity were dizziness, dry mouth, somnolence, nasal congestion, fatigue, sedation, and tachycardia; in general, for these AEs, frequency was higher with higher doses, resulting in a lower number needed to harm. Conclusions Consistent with product labeling, Iloperidone 10–16 mg/day or 20–24 mg/day demonstrated significant improvement over placebo on BPRSd and PANSS-T scores, as well as on PANSS-P and PANSS-N subscale scores over 6 weeks of treatment in patients with schizophrenia and in the ITT population, which includes patients with schizoaffective disorder. Iloperidone did not differ from placebo in terms of extrapyramidal disorders and akathisia. Copyright © 2011 John Wiley & Sons, Ltd.
