Long-term Safety of Iclepertin for Schizophrenia

No longer recruiting at 392 trial locations

Overseen By Nikos Nikas

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must be taking: Antipsychotics

Disqualifiers: Other DSM-5 diagnosis, Suicidal behavior, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding the long-term safety of a medication called Iclepertin for individuals with schizophrenia. It aims to assess participants' tolerance of daily Iclepertin use for a year, alongside their regular schizophrenia medication. This trial targets adults who previously participated in a CONNEX study and are living with schizophrenia. Participants should be stable outpatients and must have regular interaction with someone to join the study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that Iclepertin is likely to be safe for humans?

Research shows that iclepertin, the treatment under study for schizophrenia, is generally safe. In earlier studies, patients with schizophrenia who took iclepertin did not encounter serious safety issues. A previous study found that iclepertin was well tolerated over 12 weeks.

The medicine is already in a late stage of testing, indicating thorough safety evaluation. This should reassure those considering joining the trial. Participants in the new study will continue their regular schizophrenia medication alongside iclepertin, further ensuring safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Unlike the standard treatments for schizophrenia, which typically focus on managing symptoms with antipsychotic medications, BI 425809 targets cognitive impairment specifically. Researchers are excited because BI 425809 is thought to work by enhancing NMDA receptor function, which plays a critical role in cognitive processes. This novel approach could potentially improve cognitive function in patients with schizophrenia, offering an advancement beyond simply addressing psychotic symptoms.

What evidence suggests that Iclepertin might be an effective treatment for schizophrenia?

Research has shown that iclepertin, the investigational treatment under study in this trial, may enhance thinking skills in people with schizophrenia. In a study with 509 participants, iclepertin proved safe and led to noticeable improvements in cognitive abilities. These skills are crucial as they influence how well individuals think, learn, and remember. Participants who took iclepertin demonstrated better cognitive performance, potentially easing daily life. Overall, the safety and positive effects on cognition make iclepertin a promising option for those with schizophrenia. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take Iclepertin as tablets once a day for 1 year, alongside their normal medication for schizophrenia

1 year

13 visits (in-person), 9 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 425809

Trial Overview The 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.

How Is the Trial Designed?

Group I: Patients with cognitive impairment due to schizophrenia Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

In a 6-month study involving 5134 patients with paranoid schizophrenia, risperidone long-acting injectable (RLAI) demonstrated significant improvements in both clinical severity and patient functioning, indicating its efficacy in routine clinical practice.

The treatment was generally well-tolerated, with 20% of patients experiencing treatment-emergent adverse events, the most common being akathisia and weight gain, but overall, the study confirmed RLAI's good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders. Parellada, E., Kouniakis, F., Siurkute, A., et al.[2019]

In a study of 116 youths aged 8 to 19 with early-onset schizophrenia, only 12% continued their treatment for a full year, indicating challenges in long-term adherence to antipsychotic medications.

No significant differences in efficacy were found among the three antipsychotics (olanzapine, risperidone, and molindone), but side effects like akathisia and elevated prolactin levels were noted, highlighting the need for better treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study. Findling, RL., Johnson, JL., McClellan, J., et al.[2021]

The review highlights seven antipsychotic drugs in premarketing development, noting that Asenapine may improve negative and cognitive symptoms of schizophrenia, while Bifeprunox shows potential safety advantages despite a less convincing efficacy profile.

Olanzapine pamoate depot injection has comparable efficacy to oral olanzapine but raises significant safety concerns due to risks of inadvertent intravascular injection, leading to severe side effects like excessive sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. Bishara, D., Taylor, D.[2018]

Iloperidone significantly reduced relapse rates in schizophrenia patients, with a relapse rate of 20.4% for those on iloperidone compared to 63.4% for those on placebo, demonstrating its effectiveness in preventing relapse over a 26-week period.

The safety profile of iloperidone was consistent with previous studies, showing low rates of extrapyramidal symptoms and akathisia, with common side effects including dizziness (11.6%) and somnolence (8.3%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study. Weiden, PJ., Manning, R., Wolfgang, CD., et al.[2022]

An 8-week clinical trial found that adjunctive treatment with lovastatin (20 mg/day) did not improve symptoms of schizophrenia compared to placebo, as measured by the Positive and Negative Syndrome Scale (PANSS).

The study reported no serious adverse events, indicating that lovastatin was well tolerated, although participants taking lovastatin required a higher dose of risperidone for symptom management compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lovastatin for the adjunctive treatment of schizophrenia: a preliminary randomized double-blind placebo-controlled trial. Ghanizadeh, A., Rezaee, Z., Dehbozorgi, S., et al.[2018]

In a phase 2b study involving 197 patients with schizophrenia, paliperidone palmitate (PP) demonstrated significant efficacy in reducing symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), with improvements seen as early as day 8 and maintained throughout the study.

PP was generally well-tolerated, with a lower discontinuation rate due to adverse events (2% for PP vs. 10% for placebo) and comparable rates of extrapyramidal symptoms, indicating a favorable safety profile for this long-acting injectable treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study. Kramer, M., Litman, R., Hough, D., et al.[2022]

Paliperidone extended-release tablets (3-12 mg/day) were effective in maintaining symptom improvements in schizophrenia patients over a 52-week open-label extension phase, following initial 6-week placebo-controlled trials involving 1083 participants.

The treatment was generally well tolerated, with common side effects including insomnia, headache, and akathisia, while serious adverse events occurred in 16% of patients, including two suicides, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies. Emsley, R., Berwaerts, J., Eerdekens, M., et al.[2015]

In a clinical safety review involving 2500 patients treated with olanzapine for acute schizophrenia, the overall discontinuation rate was low, indicating good tolerability of the medication.

While olanzapine was associated with some significant adverse effects such as somnolence, weight gain, and elevated liver enzymes, it showed minimal risk for parkinsonism, akathisia, and no cases of hematotoxicity, making it a relatively safe option compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of olanzapine. Beasley, CM., Tollefson, GD., Tran, PV.[2018]

Iloperidone showed long-term efficacy equivalent to haloperidol in preventing relapse in schizophrenia, based on a study involving 473 patients after a 6-week stabilization phase followed by a 46-week maintenance phase.

In terms of safety, iloperidone had a more favorable profile with fewer extrapyramidal symptoms compared to haloperidol, making it a potentially better option for long-term maintenance therapy in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia. Kane, JM., Lauriello, J., Laska, E., et al.[2022]

Paliperidone extended-release (ER) significantly improved symptoms of schizophrenia over 48 weeks, with similar effectiveness in patients switching from risperidone or other antipsychotics, as measured by the Positive and Negative Syndrome Scale (PANSS).

The treatment was generally well-tolerated, with improvements in extrapyramidal symptoms and subjective side effects, although akathisia and weight gain were noted as common adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of flexibly dosed paliperidone extended-release: comparison among patients with schizophrenia switching from risperidone and other antipsychotic agents. Kim, EY., Chang, SM., Shim, JC., et al.[2015]

Iloperidone has been shown to be effective in treating schizophrenia, with multiple dosing groups demonstrating significant improvements over placebo in three randomized, double-blind studies involving 1943 patients.

Iloperidone was associated with a lower risk of motor-related side effects compared to other antipsychotics like risperidone and haloperidol, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies. Potkin, SG., Litman, RE., Torres, R., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2215001324000416

Efficacy and safety of iclepertin (BI 425809) with adjunctive ... Cognitive impairment associated with schizophrenia (CIAS) predicts poor functional outcomes (Halverson et al., 2019), is likely a barrier to medication ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10661489/

Efficacy and safety of iclepertin (BI 425809) in patients with ... A 12-wk, Phase II trial (NCT02832037) in 509 patients (pts) with schizophrenia demonstrated that iclepertin was well tolerated and significantly improved ...

3. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/mental-health/schizophrenia/update-phase-iii-connex-clinical-program-schizophrenia

Update Phase III CONNEX clinical program schizophrenia Phase II trial results demonstrated improvement in cognition with BI 425809 in adult patients with schizophrenia. Read more. Share to ...

4. nature.com nature.com/articles/s41398-022-02096-5

A Phase II substudy of patients treated with iclepertin (BI ... Patients with schizophrenia experience cognitive impairment related to neural network dysfunction and deficits in sensory processing.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10465677/

Development of the novel GlyT1 inhibitor, iclepertin (BI ... A Phase II study has demonstrated that iclepertin is safe and well tolerated in patients with schizophrenia and improves cognition at doses of ...