ITI-1284 for Anxiety

Overseen By ITI Clinical Trials

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Verified Trial

Recruiting

Sponsor: Intra-Cellular Therapies, Inc.

Disqualifiers: Schizophrenia, Bipolar, Suicidal risk, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of ITI-1284 as monotherapy treatment in patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for GAD in patients who have had inadequate response to generalized anxiety disorder treatment.

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.

What data supports the effectiveness of the drug ITI-1284 for anxiety?

The research does not provide direct evidence for the effectiveness of ITI-1284 for anxiety, but it mentions that GABAergic agents, which affect the same brain system as some anxiety medications, have shown effectiveness in reducing anxiety-like behaviors in tests. This suggests that drugs affecting similar pathways might be effective for anxiety. ^{1 2 3 4 5}

Is ITI-1284 (deuterated lumateperone) safe for humans?

Lumateperone, which is similar to ITI-1284, has been shown to have a favorable safety profile in studies for schizophrenia and other conditions, with mild side effects like drowsiness and dry mouth. It does not cause significant movement disorders or hormonal changes, making it generally safe for human use. ^{6 7 8 9 10}

What makes the drug ITI-1284 unique for treating anxiety?

ITI-1284, also known as deuterated lumateperone, is unique because it is a modified version of lumateperone that may offer improved stability and effectiveness. It potentially acts on serotonin receptors, which are involved in mood regulation, making it different from traditional anxiety treatments that often target other pathways. ^{11 12 13 14 15}

Eligibility Criteria

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?

Trial Timeline

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)

Treatment Details

Interventions

• ITI-1284 (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures. [2019]

3. France pubmed.ncbi.nlm.nih.gov

[Treatment-resistant anxiety disorders: A literature review of drug therapy strategies]. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Treatment of civilian and combat-related posttraumatic stress disorder with topiramate. [2018]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. [2020]

8. Spain pubmed.ncbi.nlm.nih.gov

Lumateperone: a new treatment approach for neuropsychiatric disorders. [2019]

9. England 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. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia. [2021]

11. Netherlands 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. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

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

13. Netherlands pubmed.ncbi.nlm.nih.gov

Acute effects of direct dopamine agonists in the mouse behavioral despair test. [2019]

14. England pubmed.ncbi.nlm.nih.gov

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

15. Netherlands pubmed.ncbi.nlm.nih.gov

Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. [2019]