Long-term Safety of Iclepertin for Schizophrenia
Recruiting in Palo Alto (17 mi)
+332 other locations
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Boehringer Ingelheim
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This study is open to adults with schizophrenia who took part in a previous CONNEX study (study 1346-0011, 1346-0012, or 1346-0013). The purpose of this study is to find out how well people with schizophrenia can tolerate a medicine called Iclepertin in the long term. Participants take Iclepertin as tablets once a day for 1 year. In addition, all participants take their normal medication for schizophrenia. Participants are in the study for a little more than 1 year. During this time, they visit the study site about 13 times and get about 9 phone calls from the study team. The doctors collect information on any health problems of the participants. Doctors also regularly check the participants' symptoms of schizophrenia.
Do I have to stop taking my current medications for this trial?
No, you can continue taking your normal medication for schizophrenia while participating in this trial.
What data supports the idea that Long-term Safety of Iclepertin for Schizophrenia is an effective drug?
The available research does not provide specific data on the effectiveness of Iclepertin for schizophrenia. Instead, it discusses other drugs like iloperidone, risperidone, and paliperidone, which have shown effectiveness in treating schizophrenia. For example, iloperidone was found to be as effective as haloperidol in preventing relapse and had fewer motor-related side effects. Risperidone long-acting injectable was also shown to be effective and well-tolerated in routine clinical practice. However, there is no direct information on Iclepertin's effectiveness for schizophrenia in the provided data.12345
What existing safety data is available for Iclepertin (BI 425809) in treating schizophrenia?
The provided research does not contain safety data for Iclepertin (BI 425809) in the treatment of schizophrenia. The studies focus on other antipsychotic medications such as iloperidone, olanzapine, paliperidone, and risperidone, evaluating their safety and efficacy in treating schizophrenia. To find safety data for Iclepertin, one would need to look for specific studies or clinical trials involving this particular treatment.12678
Is the drug Iclepertin a promising treatment for schizophrenia?
The drug Iclepertin, also known as BI 425809, is considered promising for treating schizophrenia because it is part of a new wave of treatments being developed to address safety and effectiveness concerns with current options. It represents a potential advancement in providing better treatment for schizophrenia.1691011
Eligibility Criteria
This trial is for adults with schizophrenia who previously participated in a CONNEX study. They must be clinically stable, use effective birth control if applicable, and have a regular caregiver or partner to interact with them. People can't join if they've had repeated positive drug screens, developed conditions other than schizophrenia that would interfere with the trial, or shown severe suicidal behavior recently.Inclusion Criteria
I have been diagnosed with schizophrenia and am stable.
Patients who completed participation in the parent trial
I have someone who regularly helps me and can be involved in the study.
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Exclusion Criteria
Participant developed DSM-5 diagnosis other than Schizophrenia or any condition preventing participation in the extension trial since enrolment into the parent phase III trial
Patients currently or wishing to participate in another investigational drug trial
Any suicidal behavior and/or suicidal ideation of type 5 based on the C-SSRS in parent trial and up to and including Visit 1 of this study
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Treatment Details
Interventions
- BI 425809 (Other)
Trial OverviewThe study tests the long-term safety of Iclepertin tablets taken daily for one year by people with schizophrenia while continuing their normal medication. Participants will visit the study site approximately 13 times and receive around 9 calls from researchers over slightly more than a year.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Patients with cognitive impairment due to schizophreniaExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford University Medical CenterStanford, CA
ATP Clinical Research, Inc.Orange, CA
Institute of LivingHartford, CT
Omaha Insomnia and Psychiatric ServicesOmaha, NE
More Trial Locations
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Who Is Running the Clinical Trial?
Boehringer IngelheimLead Sponsor
References
Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia. [2022]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.
Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders. [2019]This postauthorization safety study evaluated the long-term safety, tolerability, and efficacy of risperidone long-acting injectable (RLAI) in routine clinical practice. In this 6-month, multicenter, European, naturalistic study, patients were included if, during routine clinical practice, long-term antipsychotic therapy with RLAI was deemed necessary by the treating physician. Efficacy measures included Clinical Global Impression-Severity and Global Assessment of Functioning. Safety was evaluated by recording treatment-emergent adverse events (AE). RLAI was initiated in 5134 patients (aged 14-94 years); predominantly male (58.6%) with paranoid schizophrenia (69.8%). RLAI initial doses were 25 mg every 2 weeks (37.0% patients), 37.5 mg (18.0%), and 50 mg (44.4%). Treatment was completed by 4314 patients (84.0%). RLAI was discontinued on account of loss to follow-up (n=346; 6.7%), insufficient response (n=116; 2.3%), and AEs (n=106; 2.1%). Clinical Global Impression-Severity significantly improved from baseline to endpoint (P or = 5% of patients were akathisia, extrapyramidal disorders, depression, psychotic disorder, anxiety, and weight gain. Serious AEs were reported by 384 (8%) patients. This study confirms good safety, tolerability, and efficacy with RLAI in routine clinical practice.
Long-term effectiveness of flexibly dosed paliperidone extended-release: comparison among patients with schizophrenia switching from risperidone and other antipsychotic agents. [2015]The current study compared the long-term effectiveness, safety, and tolerability of paliperidone extended-release (ER) among patients with schizophrenia who had switched from risperidone (risperidone group) or other antipsychotic medications (non-risperidone group) due to lack of efficacy, intolerability, or non-adherence.
Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies. [2022]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.
Lovastatin for the adjunctive treatment of schizophrenia: a preliminary randomized double-blind placebo-controlled trial. [2018]While statins target many of the pathways to neuroprogression in schizophrenia, the safety and efficacy of statins for treating schizophrenia has never been examined. This is an 8-week randomized double blind controlled clinical trial examining the efficacy and safety of adjunctive lovastatin (20 mg/day) treatment or placebo for people with schizophrenia. The baseline characteristics of the two groups were not different. Endpoint changes in Positive and Negative Syndrome Scale (PANSS) total and subscale scores did not differ between the two groups. However there was a significant difference between the doses of risperidone used in the two groups. The mean dose in the lovastatin and placebo groups were 4.8(1.8) and 3.4(1.4) mg/day, respectively (P
Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies. [2015]Long-term efficacy and safety of paliperidone extended-release tablets (3-12 mg/day) were evaluated in pooled data from 52-week open-label extension (OLE) phases of three 6-week, placebo-controlled, double-blind (DB) trials involving 1083 schizophrenia patients. Forty-seven percent of patients completed the OLE phase. Outcome measures included Positive and Negative Syndrome Scale and Personal and Social Performance scale scores. Improvements observed on both scales in active treatment groups during the DB phases were maintained during the OLE phase. Most commonly (> or =10% patients) reported adverse events (AEs) were insomnia, headache, and akathisia. One or more serious AEs were reported by 16% of patients; two patients had a treatment-emergent AE that resulted in death (suicide). Extrapyramidal symptom-related AEs were reported by 25% of patients. Median maximum movement disorder rating scale scores indicated no severity change during the OLE. Mean (+/-SD) increase in body weight from OLE baseline to end point was 1.1+/-5.47 kg across treatment groups and there were no clinically meaningful changes for plasma glucose, insulin or lipid levels. This analysis shows that paliperidone extended-release can maintain improvements in symptoms and functioning and is generally well tolerated for up to 52 weeks in schizophrenia patients.
Safety of olanzapine. [2018]Clinical safety data for treatment of acute schizophrenia with olanzapine, a new atypical antipsychotic agent, are summarized. The primary clinical trial safety database included 2500 patients treated with olanzapine, 810 with haloperidol, and 236 with placebo. The overall discontinuation rate from olanzapine treatment was low. Significant adverse events included somnolence, weight gain, and asymptomatic treatment-emergent transaminase elevation. Minimal parkinsonism and akathisia with rare dystonia were noted. No hematotoxicity was noted. The incidence of seizures and sexual dysfunction was rare.
Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study. [2022]We evaluated the efficacy and safety of the investigational long-acting injectable antipsychotic agent paliperidone palmitate (PP) in the treatment of schizophrenia. Patients were randomized to receive gluteal injections of placebo or PP (50 or 100 mg eq., fixed doses), without oral supplementation, on days 1, 8, and 36 (9-wk, double-blind phase) in this phase 2b study. Patients (n=197, intent-to-treat analysis set) were 62% men, mean (s.d.) age 39 (10) yr, with a baseline mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total score of 87.0 (12.5). Mean (s.d.) PANSS total scores showed significant improvement at endpoint (primary measure) for both the PP 50 mg eq. [-5.2 (21.5)] and PP 100 mg eq. [-7.8 (19.4)] groups, vs. placebo [6.2 (18.3)] (p0.001, each dose vs. placebo). This improvement was detected by day 8 and maintained to endpoint (p0.011) for both doses. In the safety analysis set (n=247), fewer PP-treated patients (2%) discontinued for treatment-emergent adverse events vs. placebo-treated (10%). Rates of treatment-emergent extrapyramidal syndrome-related adverse events were comparable between active treatment and placebo, with the exception of parkinsonism-related disorders (50 mg eq. 5%, 100 mg eq. 8%, placebo 1%). Results of other safety measures suggest PP to be generally well-tolerated. Throughout the study, investigators rated injection-site pain as absent (56-71%), mild (24-39%), moderate (2-12%), or severe (0-2%). PP (50 and 100 mg eq. doses) administered as a gluteal intramuscular injection was efficacious and generally tolerated in these patients with acute symptomatic schizophrenia.
Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study. [2021]To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders.
Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. [2018]Since the introduction of a group of atypical antipsychotics in the 1990s, there has been a decline in the rate of new antipsychotics being introduced into clinical practice. However, with increasing safety and efficacy concerns over currently available drugs and a dearth of options available for atypical depot formulations, there is a considerable need for the development of new formulations and agents. This review examines the profile of seven antipsychotic drugs currently in the premarketing stage of development and summarizes their mechanism of action, clinical potential and safety.Asenapine is an antipsychotic with activity for multiple receptors and has potential to improve negative and cognitive symptoms of schizophrenia. Bifeprunox is a partial dopamine D2 and serotonin 5-HT(1A) receptor agonist showing a less than convincing efficacy profile, but which may offer safety advantages over available agents by means of a reduced risk of metabolic complications. Iloperidone is a D2 and 5-HT(2A) receptor antagonist requiring further studies to establish its effectiveness. It has a high affinity for alpha(1)-adrenoceptors, which can lead to associated haemodynamic adverse effects. Nemonapride is essentially a typical antipsychotic drug, similar in structure to sulpiride, which has been available for some time in Japan. It has efficacy against positive symptoms and has shown some antidepressant and anxiolytic properties, although efficacy data for it are somewhat limited. Norclozapine (N-desmethylclozapine) is a major metabolite of clozapine formed by its demethylation. Its partial agonist activity at D2 receptors has raised interest in it as an antipsychotic in its own right. In addition, it appears to have muscarinic agonist activity, which is believed to be responsible for the observed positive effects it has on cognition. It was envisaged to be effective as an adjunct to other agents or at high doses in the treatment of refractory schizophrenia, although a recent randomized, controlled study showed that it was no more effective than placebo in patients with schizophrenia experiencing an acute psychotic episode. Olanzapine pamoate depot injection has shown comparable efficacy to oral olanzapine in several studies. However, it has provoked considerable safety concerns by its association with inadvertent intravascular injection events in numerous patients. This accidental intravascular administration of olanzapine pamoate leads to excessive sedation, confusion, dizziness and altered speech. Post-injection observation periods and postmarketing surveillance are planned following the introduction of the depot. Paliperidone palmitate is the palmitate ester of paliperidone, the major metabolite of risperidone, and is formulated as a long-acting injection for intramuscular use. Its pharmacology is comparable to risperidone, having D2 and 5-HT(2A) receptor antagonist activity. Efficacy studies have shown positive results, and because paliperidone has no antagonistic activity at cholinergic receptors, it has low potential for anticholinergic adverse effects, including cognitive dysfunction. However, with higher doses, the frequency of extrapyramidal side effects and orthostatic hypotension have been shown to be greater than with placebo.
A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study. [2022]The purpose of this study was to evaluate the safety and effectiveness of iloperidone for the prevention of relapse in schizophrenia.