Adjunctive Troriluzole for OCD

No longer recruiting at 94 trial locations

Overseen By Jim Mather

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Biohaven Pharmaceuticals, Inc.

Must be taking: SSRIs, Clomipramine

Disqualifiers: Bipolar, Schizophrenia, Autism, others

Stay on Your Current Meds You can continue your current medications while participating

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: 5

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether troriluzole, a new potential drug, can help manage symptoms for people with Obsessive Compulsive Disorder (OCD) when added to their current medication. Participants will receive either troriluzole or a placebo to compare effectiveness and safety. It suits those who have had OCD for at least a year and have not found much success with standard medications like SSRIs, a common type of antidepressant. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in OCD treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, you must have an inadequate response to your current OCD medication, which should be a selective serotonin reuptake inhibitor (excluding fluvoxamine) or clomipramine, taken at a stable dose for at least 8 weeks before screening and 12 weeks at baseline.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it requires that you have been on a stable dose of a selective serotonin reuptake inhibitor (excluding fluvoxamine) or clomipramine for at least 12 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that troriluzole is generally safe for people. Studies have found it does not harm the liver, which is crucial for overall health. Trials have also tested its use in people with obsessive-compulsive disorder (OCD) who continue to experience symptoms despite other treatments. So far, these studies have identified no major safety issues.

While any treatment carries some risk, available information suggests that troriluzole is safe for people with OCD. However, individual experiences can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

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

Troriluzole is unique because it offers a novel approach to treating OCD by modulating glutamate levels in the brain, which is different from most current treatments that primarily target serotonin pathways, like SSRIs. This mechanism could provide relief for those who don't respond well to existing medications. Researchers are excited because Troriluzole's potential to address treatment-resistant OCD could significantly improve the quality of life for many patients.

What evidence suggests that troriluzole might be an effective treatment for OCD?

Research has shown that troriluzole, one of the treatments under study in this trial, may aid individuals with Obsessive Compulsive Disorder (OCD) who haven't improved with standard therapies. One study found that patients taking troriluzole consistently showed better OCD symptoms over time. Those with more severe OCD seemed to benefit even more from the treatment. These findings suggest that troriluzole could enhance the effects of existing OCD treatments. Participants in this trial will receive either troriluzole or a placebo to further evaluate its effectiveness. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with Obsessive Compulsive Disorder (OCD) who haven't had enough improvement with standard treatments like certain antidepressants. They should be medically stable and able to complete the study, without a history of severe mental health disorders or brain injuries.

Inclusion Criteria

You have been diagnosed with obsessive-compulsive disorder (OCD) for at least one year, as confirmed by a mental health assessment.

An inadequate response to current Standard of Care medication defined as selective serotonin reuptake inhibitor (excluding fluvoxamine) or clomipramine treatment at an adequate and stable dose for at least 8 weeks prior to screening and at least 12 weeks at baseline (adequate dose defined by USPI labeling); an inadequate response too current standard of car base on the YBOCS score.

Determined by the investigator to be medically stable at baseline/ randomization as assessed by medical history, physical examination, laboratory test results, and electrocardiogram testing. Subjects must be physically able and expected to complete the trail as designed.

Exclusion Criteria

Subjects with a history of more than two (2) previous failed or inadequate treatment classes given for an adequate duration at an adequate dose as defined by the MGH-TRQ-OCD.

Are you currently on a medication for your mental health?

Answer YES if you have NOT had a stroke, seizure, or traumatic brain injury?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive either Troriluzole or placebo for 10 weeks, with dosage adjustments after the first two weeks

10 weeks

4 visits (in-person) at baseline, week 4, 8, and 10

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Troriluzole

Trial Overview The trial is testing Troriluzole as an added treatment against a placebo in people with OCD. The goal is to see if it's effective and safe when used alongside current medications that aren't working well enough.

How Is the Trial Designed?

Group I: Troriluzole Experimental Treatment 1 Intervention

Troriluzole- 2 100mg capsules once daily for the first two weeks. Troriluzole- 2 140mg capsules once daily from week two through week ten.

Group II: Placebo Placebo Group 1 Intervention

Placebo- 2 100mg capsules once daily for the first two weeks. Placebo- 2 140mg capsules once daily from week two through week ten.

Who Is Running the Clinical Trial?

Biohaven Pharmaceuticals, Inc.

Lead Sponsor

Trials

49

Recruited

30,100+

Published Research Related to This Trial

In an 8-week randomized trial with 50 patients, adding riluzole to fluvoxamine treatment significantly improved symptoms of moderate to severe obsessive-compulsive disorder, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

The study found that patients receiving riluzole showed a greater reduction in both total Y-BOCS scores and the Compulsive subscale scores compared to those receiving fluvoxamine plus placebo, indicating that riluzole may enhance the efficacy of fluvoxamine in treating OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riluzole in augmentation of fluvoxamine for moderate to severe obsessive-compulsive disorder: Randomized, double-blind, placebo-controlled study. Emamzadehfard, S., Kamaloo, A., Paydary, K., et al.[2022]

In a pilot study involving 38 patients with obsessive-compulsive disorder (OCD) who were not responding well to standard serotonin reuptake inhibitors (SRIs), riluzole was found to be well tolerated with minimal side effects, suggesting it is a safe option for augmentation therapy.

While the overall improvement in OCD symptoms with riluzole did not reach statistical significance, there was a notable trend indicating potential benefits, particularly in outpatients, where more patients experienced at least a 25% improvement compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot randomized placebo-controlled trial. Pittenger, C., Bloch, MH., Wasylink, S., et al.[2022]

In a 4-week study involving 30 patients with endogenous depression, trazodone was found to be as effective as imipramine and significantly better than a placebo, showing antidepressant effects as early as 7 days into treatment.

Trazodone had fewer side effects, particularly anticholinergic effects, compared to imipramine, and its antidepressant effects were sustained for at least 5 months after the initial treatment phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled study of trazodone, imipramine, and placebo in outpatients with endogenous depression. Mann, JJ., Georgotas, A., Newton, R., et al.[2019]

The new compound deschloroclozapine (DCZ) offers improved control over neuronal activity when used with designer receptors (DREADDs), showing higher potency and reduced off-target effects compared to the previously used clozapine-N-oxide (CNO).

DCZ allows for faster modulation of brain function in living animals, addressing the limitations of CNO's slow action and potential side effects, making it a more reliable tool for studying neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A novel ligand for chemogenetic receptors, Deschloroclozapine, enables rapid and selective modulation of neuronal activity and behavior in living animals]. Nagai, Y.[2022]

In a study of 20 patients with treatment-resistant obsessive-compulsive disorder (OCD), adding amisulpiride to ongoing selective serotonin reuptake inhibitor (SRI) treatment resulted in a significant reduction in OCD symptoms, as measured by the Yale-Brown obsessive-compulsive scale (Y-BOCS).

Common side effects of amisulpiride included weight gain (70% of patients), mild sedation (65%), and asthenia (35%), indicating that while amisulpiride may be effective, it also carries notable risks that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amisulpiride augmentation in treatment resistant obsessive-compulsive disorder: an open trial. Metin, O., Yazici, K., Tot, S., et al.[2022]

In a 12-week open-label trial involving 6 children aged 8-16 with treatment-resistant OCD, 4 out of 6 subjects showed significant improvement in symptoms, with a reduction of over 46% on the Children's Yale-Brown Obsessive-Compulsive Scale.

Riluzole was well tolerated, with no adverse effects leading to discontinuation, and all participants chose to continue the medication after the trial, suggesting its potential as a safe alternative treatment for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. Grant, P., Lougee, L., Hirschtritt, M., et al.[2022]

Teflutixol, a new thioxanthene derivative, was administered to 21 patients over 4 weeks, showing significant improvement in symptoms for patients with schizophrenia and obsessive-compulsive neurosis, as measured by the Brief Psychiatric Rating Scale (BPRS).

The treatment was well-tolerated, with most patients receiving a low daily dose of 1 mg or less, indicating that teflutixol may be an effective and safe option for managing these psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teflutixol (Lu 10-022): a new thioxanthene derivative with antipsychotic properties. A pilot study. Botte, L.[2012]

In a study of 13 patients with treatment-resistant obsessive-compulsive disorder (OCD), the addition of riluzole significantly improved OCD symptoms, with 54% of participants showing over a 35% reduction in their Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores.

Riluzole was well tolerated and also led to significant improvements in depression and anxiety symptoms, suggesting it could be a beneficial augmentation therapy for patients who do not respond fully to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Coric, V., Taskiran, S., Pittenger, C., et al.[2013]

New classes of triple reuptake inhibitors have been developed, showing high potency and selectivity for serotonin, norepinephrine, and dopamine transporters, which are important for treating mood disorders.

One promising compound, derivative 15, demonstrated good oral bioavailability and effective brain penetration in rats, making it a strong candidate for further development in treating depression or related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes: a new series of potent and selective triple reuptake inhibitors. Micheli, F., Cavanni, P., Arban, R., et al.[2014]

Obsessive-compulsive disorder (OCD) affects about 1 in 40 people in the U.S., and recent studies show that it can respond to drug treatments, particularly selective serotonin uptake inhibitors like clomipramine and fluoxetine.

Emerging research suggests that buspirone, which has anxiolytic and potential antidepressant effects, may provide direct benefits for OCD patients or enhance the effects of fluoxetine when used together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obsessive-compulsive disorder: treatment with serotonin-selective uptake inhibitors, azapirones, and other agents. Murphy, DL., Pato, MT., Pigott, TA.[2013]

Compound 4, a trifluoromethanesulfonyloxy analogue of clozapine, shows higher affinity for dopamine D2 receptors compared to clozapine, indicating potential for enhanced efficacy in treating conditions like schizophrenia.

Unlike clozapine, compound 4 does not exhibit anticholinergic properties, which may lead to fewer side effects, making it a promising new neuroleptic candidate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine: identification of a novel atypical neuroleptic. Liao, Y., DeBoer, P., Meier, E., et al.[2013]

In a study of 11 OCD patients who did not respond well to SSRIs and previous atypical antipsychotics, adding aripiprazole to their treatment resulted in significant improvement, with 7 out of 10 completers showing over a 35% reduction in OCD symptoms after 12 weeks.

While aripiprazole appears to be an effective augmentation strategy for treatment-resistant OCD, the study also noted some adverse events, highlighting the need for further research to confirm these findings and assess long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case series of aripiprazole augmentation of selective serotonin reuptake inhibitors in treatment-refractory obsessive compulsive disorder. Matsunaga, H., Hayashida, K., Maebayashi, K., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03299166

Troriluzole (BHV-4157) in Adult Participants With ... The purpose of this study is to evaluate the efficacy of troriluzole as adjunctive therapy versus placebo in participants with obsessive compulsive disorder ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04708834

Long-term Safety Study of Adjunctive Troriluzole in ... The purpose of the study is to evaluate the long term safety and tolerability of troriluzole as adjunctive therapy in subjects with obsessive compulsive ...

3. prnewswire.com prnewswire.com/news-releases/biohaven-announces-obsessive-compulsive-disorder-ocd-proof-of-concept-phase-23-study-results-and-program-update-301082586.html

Biohaven Announces Obsessive-Compulsive Disorder ... Troriluzole 200 mg administered once daily as adjunctive therapy in OCD patients with inadequate response to standard of care treatment showed consistent ...

4. biohaven.com biohaven.com/wp-content/uploads/ASCP-2024-poster-troriluzole-OCD.pdf

ASCP-2024-poster-troriluzole-OCD.pdf A Phase 2 study of troriluzole in OCD demonstrated consistent treatment benefit at all timepoints. Patients with more severe OCD symptoms at.

5. withpower.com withpower.com/trial/phase-3-disease-11-2020-6284b

Troriluzole for Obsessive-Compulsive Disorder This trial is for individuals with Obsessive-Compulsive Disorder (OCD) who haven't had enough improvement with standard treatments like certain antidepressants.

6. biohaven.com biohaven.com/wp-content/uploads/BioH-TRO-HepaticSafety-POS-AAN-Final_4-12-24.pdf

Troriluzole Exhibits Favorable Hepatic Safety Profile ... This analysis assesses the hepatic safety profile of troriluzole in pooled clinical trial data, inclusive of data on participants with obsessive ...

7. ctv.veeva.com ctv.veeva.com/study/efficacy-and-safety-study-of-adjunctive-troriluzole-in-obsessive-compulsive-disorder

Efficacy and Safety Study of Adjunctive Troriluzole in ... The study's purpose is to evaluate the efficacy and safety of troriluzole as adjunctive therapy compared to placebo in subjects with ...