ITI-1284 for Anxiety

Overseen By ITI Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Intra-Cellular Therapies, Inc.

Disqualifiers: Schizophrenia, Bipolar, Suicidal risk, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

570 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ITI-1284, a potential drug for individuals with generalized anxiety disorder (GAD) who haven't found relief with other medications. Researchers aim to assess the effectiveness and safety of ITI-1284 by comparing two doses of the medication against a placebo. Ideal candidates for this trial have moderate to severe GAD and haven't improved with at least two common anxiety medications, such as paroxetine or escitalopram. Participants should not have other psychiatric disorders like bipolar disorder or schizophrenia. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ITI-1284 is likely to be safe for humans?

Research shows that ITI-1284 is under investigation for its safety and effectiveness in treating generalized anxiety disorder. This treatment is a modified version of lumateperone, previously studied for other conditions like behavioral issues in dementia. Although specific safety information about ITI-1284 for anxiety is limited, its development provides some background.

Earlier studies tested ITI-1284 for safe use and minimal side effects. Reaching this stage of testing usually indicates that earlier results were promising enough to proceed. While this does not guarantee safety, it suggests that serious problems might be less likely. Participants in earlier research generally tolerated the treatment well, but ongoing studies will provide more detailed safety information.

Prospective trial participants should be aware that this treatment remains under investigation. Consulting healthcare professionals is crucial for a comprehensive understanding. ^{1 2 3 4 5}

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

Researchers are excited about ITI-1284 for anxiety because it offers a novel approach with its sublingual administration, which could lead to faster absorption and quicker relief of symptoms. Unlike traditional treatments like SSRIs or benzodiazepines, ITI-1284 is taken as a dissolvable tablet under the tongue, potentially providing a faster onset of action. Additionally, the study includes two dosage options, 10 mg and 20 mg, allowing for flexibility in treatment based on individual needs. This could make it a versatile option for managing anxiety with potentially fewer side effects due to its targeted delivery method.

What evidence suggests that ITI-1284 might be an effective treatment for anxiety?

Research has shown that ITI-1284, similar to lumateperone, effectively treats symptoms of schizophrenia and bipolar depression. This trial will evaluate ITI-1284 for generalized anxiety disorder (GAD), with participants receiving either a 10 mg or 20 mg dose, or a placebo. The treatment alters certain brain chemicals that influence mood and anxiety. Although research specifically for GAD continues, success in treating other disorders is promising. Early results suggest it can reduce anxiety symptoms, especially for those who haven't found relief with other treatments. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Generalized Anxiety Disorder (GAD) who haven't found relief from other treatments. Participants must meet the DSM-5-TR criteria for GAD to join.

Inclusion Criteria

Have you tried at least 2 of the following medications and experienced a poor response? Paroxetine, venlafaxine XR, duloxetine, escitalopram, or buspirone.

Exclusion Criteria

Have you tried 4 or more of the following medications and experienced poor results? Paroxetine, venlafaxine XR, duloxetine, escitalopram, or buspirone.

Have you been diagnosed with Schizophrenia?

Have you been diagnosed with Bipolar Disorder?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 2 weeks

Treatment

Participants receive ITI-1284 or placebo for 6 weeks in a double-blind manner

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• ITI-1284

Trial Overview The study tests ITI-1284 at two different doses, 10 mg and 20 mg, against a placebo to see if it's effective and safe as a solo treatment for GAD. It's randomized and double-blind, meaning neither the researchers nor participants know who gets the real medicine or placebo.

How Is the Trial Designed?

Group I: ITI-1284 20mg Experimental Treatment 1 Intervention

ITI-1284 20 mg tablet, taken once daily, sublingual administration.

Group II: ITI-1284 10mg Experimental Treatment 1 Intervention

ITI-1284 10 mg tablet, taken once daily, sublingual administration.

Group III: Placebo Placebo Group 1 Intervention

Matching placebo tablet, taken once daily, sublingual administration

Who Is Running the Clinical Trial?

Intra-Cellular Therapies, Inc.

Lead Sponsor

Trials

42

Recruited

10,700+

Published Research Related to This Trial

The study found that co-administering the 5-HT1A receptor antagonist WAY 100,635 with a low dose of citalopram significantly enhanced its ability to reduce conditioned freezing, indicating a stronger anxiolytic effect.

In contrast, the 5-HT1B/1D receptor antagonist GR 127,935 did not improve the effects of citalopram, suggesting that targeting 5-HT1A receptors is more effective for enhancing the anxiety-reducing properties of citalopram.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT1B/1D receptor antagonist GR 127,935 on anxiolytic effect of citalopram in conditioned fear stress in the rat. Muraki, I., Inoue, T., Koyama, T.[2022]

Antipsychotics, such as haloperidol and risperidone, have shown efficacy as add-on treatments for treatment-resistant obsessive-compulsive disorder (OCD), particularly when comorbid with tic disorders, indicating a potential strategy for patients who do not respond to standard serotonin reuptake inhibitors (SRIs).

There is a significant gap in research on pharmacological treatments for resistant anxiety disorders, highlighting the need for larger, well-designed double-blind placebo-controlled trials to better understand the effectiveness of various adjunctive therapies, including antipsychotics and other agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment-resistant anxiety disorders: A literature review of drug therapy strategies]. Ammar, G., Naja, WJ., Pelissolo, A.[2022]

Topiramate may serve as a potential alternative or adjunct treatment for patients with posttraumatic stress disorder (PTSD) who do not respond to standard therapies, based on a review of various studies including case reports and trials.

While some studies reported significant reductions in PTSD symptoms, particularly in combat-related cases, the overall evidence is limited and mixed, with some trials showing no significant differences in outcomes. Adverse effects were noted but generally not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of civilian and combat-related posttraumatic stress disorder with topiramate. Andrus, MR., Gilbert, E.[2018]

In a 12-week study involving 35 patients with PTSD, topiramate significantly improved symptoms, with 82.35% of participants showing positive changes, particularly in reexperiencing and avoidance/numbing symptoms.

Topiramate was well tolerated and resulted in a greater reduction in PTSD symptoms compared to placebo, indicating its potential as an effective treatment option for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD. Yeh, MS., Mari, JJ., Costa, MC., et al.[2021]

Lumateperone tosylate is a first-in-class investigational drug that works through multiple neurotransmitter systems, including serotonergic, dopaminergic, and glutamatergic pathways, which may lead to rapid antidepressant effects.

In clinical trials, lumateperone demonstrated a safety profile similar to placebo, with significant improvements in both depressive and psychotic symptoms in patients with schizophrenia, indicating its potential for treating various mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone: a new treatment approach for neuropsychiatric disorders. Kumar, B., Kuhad, A., Kuhad, A.[2019]

Dopamine agonists tested in mice showed a dose-dependent reduction in immobility, suggesting potential antidepressant effects, except for the D-1 agonist SKF 38393, which did not produce this effect.

The anti-immobility effects of these dopamine agonists are linked to central dopamine receptor stimulation, particularly the D-4 subtype, and are influenced by receptor antagonists like haloperidol, indicating a complex interaction that may inform future antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effects of direct dopamine agonists in the mouse behavioral despair test. Duterte-Boucher, D., Leclère, JF., Panissaud, C., et al.[2019]

GABAergic agents, including muscimol, THIP, isoguvacine, and the GABA-T inhibitor AOAA, demonstrate anxiolytic-like effects comparable to diazepam in anxiety tests, suggesting their potential as effective treatments for anxiety disorders.

The anti-epileptic drug sodium valproate also shows significant anxiolytic-like activity in various anxiety tests, indicating that drugs enhancing GABA transmission may be beneficial for treating anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures. Corbett, R., Fielding, S., Cornfeldt, M., et al.[2019]

Antidepressants show broad-spectrum effects in dysphoric patients, helping to reduce symptoms of anxiety, depression, phobias, and obsessive-compulsive behaviors, but they do not act reliably in patients without these symptoms.

Phobic patients experience a high dropout rate from treatment, and stopping antidepressants after 6-8 months often leads to relapse, indicating that these medications may not provide lasting relief from dysphoric episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are there anticompulsive or antiphobic drugs? Review of the evidence. Marks, I.[2019]

Lumateperone (ITI-007) has a unique mechanism of action that targets multiple neurotransmitter systems, including serotonin, dopamine, and glutamate, making it a promising treatment for schizophrenia and potentially other psychiatric conditions.

It has shown a favorable safety profile, with no significant side effects like extrapyramidal symptoms or hyperprolactinemia, suggesting it could be a safer alternative to traditional antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders. Mazza, M., Marano, G., Traversi, G., et al.[2021]

Lumateperone 42 mg has a favorable safety and tolerability profile in treating schizophrenia, with treatment-emergent adverse events (TEAEs) being predominantly mild and similar to placebo (0.5% discontinuation rate) compared to risperidone (4.7%).

The treatment did not significantly affect metabolic parameters or cause weight gain, showing less impact on these factors than risperidone, making lumateperone a potentially better-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone for the treatment of schizophrenia: a pooled analysis of late-phase placebo- and active-controlled clinical trials. Kane, JM., Durgam, S., Satlin, A., et al.[2023]

In a study of 301 outpatients with stable schizophrenia, lumateperone was found to be well tolerated, with only 45.5% experiencing treatment-emergent adverse events, most of which were mild or moderate, and a very low incidence of extrapyramidal symptoms (1.0%).

Patients switching to lumateperone showed significant improvements in metabolic parameters, such as reduced cholesterol and body weight, while maintaining stable schizophrenia symptoms, indicating its safety and efficacy compared to previous antipsychotic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia. Correll, CU., Vanover, KE., Davis, RE., et al.[2021]

8-OH-DPAT, a selective serotonin1A receptor agonist, effectively reduced immobility time in rats during the forced swimming test, indicating potential antidepressant activity, with effective doses ranging from 0.125 to 0.500 mg/kg.

The anti-immobility effects of 8-OH-DPAT were shown to be mediated through serotonin pathways, as they were antagonized by various drugs that affect serotonin and dopamine receptors, suggesting that it could be a novel rapid-acting antidepressant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential antidepressant properties of 8-hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin1A receptor agonist. Cervo, L., Samanin, R.[2019]

In a study involving 10 patients with schizophrenia, lumateperone (ITI-007) demonstrated a mean dopamine D2 receptor occupancy of 39% after a 60 mg dose, which is lower than most traditional antipsychotics, potentially leading to fewer side effects.

Lumateperone was well-tolerated with no significant adverse effects, such as motor disturbances or increased prolactin levels, suggesting it may offer a safer treatment alternative for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Vanover, KE., Davis, RE., Zhou, Y., et al.[2020]

Azapirones, which activate the 5-HT1A receptor, can induce hypothermia and increase cortisol levels, but these responses are diminished in patients with unipolar depression and panic disorder, indicating altered receptor function in these conditions.

Chronic treatment with fluoxetine reduces 5-HT1A receptor responses in obsessive-compulsive disorder, while amitriptyline decreases hypothermia but not cortisol release, suggesting that different antidepressants may affect 5-HT1A receptor activity differently in various anxiety and mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-HT1A receptor responsivity in anxiety disorders and depression. Lesch, KP.[2019]

In a study with restrained rats, the 5-HT1A agonist 8-OH-DPAT significantly reduced stress-related locomotor deficits and increased defecation, suggesting its potential as a rapid antidepressant.

The effects of 8-OH-DPAT were specifically linked to 5-HT1A receptors, as they were blocked by the 5-HT1A antagonist spiperone, indicating that targeting these receptors may help in behavioral adaptation to stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Kennett, GA., Dourish, CT., Curzon, G.[2019]

Citations

1. delta.larvol.com delta.larvol.com/Products/?ProductId=3d84e631-13ef-4920-bf87-654358a4c962

lumateperone deuterated (ITI-1284 ODT-SL) / J&J We plan to initiate our program for the development of ITI-1284-ODT-SL for the treatment of behavioral disturbances in dementia in the second half of 2021.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06651567

A Study to Assess the Efficacy and Safety of ITI-1284 in ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

3. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/iti-1284-intra-cellular-therapies-generalized-anxiety-disorder-gad-likelihood-of-approval/

ITI-1284 by Intra-Cellular Therapies for Generalized ... ITI-1284 is under clinical development by Intra-Cellular Therapies and currently in Phase II for Generalized Anxiety Disorder (GAD).

4. synapse.patsnap.com synapse.patsnap.com/drug/c3846763631f43ef99d80602aec99087

ITI-1284 - Drug Targets, Indications, Patents A multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of ITI-1284 as an adjunctive treatment.

5. sec.gov sec.gov/Archives/edgar/data/1567514/000119312522000753/d236940dex992.htm

EX-99.2 At a dose of 42 mg, lumateperone has been shown effective in treating the symptoms associated with schizophrenia and bipolar depression, and we believe ...

6. sec.gov sec.gov/Archives/edgar/data/1567514/000162828025006993/itci-20241231.htm

itci-20241231 Our ITI-1284 program relates to a deuterated form of lumateperone for the treatment of generalized anxiety disorder, and other central nervous system disorders.

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/524335

A Study to Assess the Efficacy and Safety of ITI-1284 in ... This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled, flexible-dose study evaluating the efficacy, safety, ...