Basimglurant for Trigeminal Neuralgia

Recruiting at29 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Noema Pharma AG

Must not be taking: Opioids, Antipsychotics

Disqualifiers: Major psychiatric, Substance abuse, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called basimglurant to see if it can help reduce severe facial pain in adults with Trigeminal Neuralgia. The medication works by blocking a specific receptor in the nervous system to lower pain signals. Researchers will measure changes in pain using patient diaries and feedback.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current TN pain medication to participate in this trial. However, you can use opioids for pain control as long as it does not exceed 2 days per week.

Is basimglurant safe for human use?

Basimglurant has been tested in humans for conditions like Fragile X syndrome and major depressive disorder. It was generally well-tolerated, but some patients experienced psychiatric side effects like hallucinations or psychosis. Overall, it has shown a favorable safety profile in clinical trials, but further studies are needed to fully understand its safety in different populations. ^{1 2 3 4 5}

How is the drug Basimglurant different from other drugs for trigeminal neuralgia?

Basimglurant is unique because it is being explored as a novel treatment option for trigeminal neuralgia, whereas traditional treatments primarily include anticonvulsant drugs like carbamazepine and oxcarbazepine. Unlike these standard treatments, Basimglurant may offer a different mechanism of action, potentially providing an alternative for patients who do not respond well to existing medications. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

Adults aged 18-75 with a confirmed diagnosis of primary trigeminal neuralgia, experiencing significant pain despite current treatments. Participants must be fluent in the study language and capable of giving informed consent. Women must be non-pregnant, non-lactating, and using contraception if of childbearing potential.

Inclusion Criteria

I have been diagnosed with trigeminal neuralgia by a neurologist.

I experience severe pain episodes daily for at least 2 months.

I experience severe pain episodes daily for at least 2 months.

Exclusion Criteria

I have had stomach or small intestine surgery, or a condition that affects how my body absorbs nutrients.

I have not taken antipsychotic medications in the last 6 months.

I haven't had a heart attack, stroke, or major heart surgery in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants receive Basimglurant once daily starting at 1.5mg for 8 weeks to evaluate its effect on pain associated with TN

8 weeks

Double-blind Treatment

Participants receive double-blind treatment with Basimglurant or placebo to assess maintenance of effect on pain

12 weeks

Open-label Extension

Participants are offered open-label treatment with Basimglurant to evaluate long-term safety and efficacy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Basimglurant (Glutamate Receptor Antagonist)

Trial Overview The trial is testing the effectiveness and safety of basimglurant (1.5mg - 3.5mg) for adults with trigeminal neuralgia compared to a placebo. The goal is to see if this medication can reduce the intense facial pain associated with TN.

Participant Groups

Group I: Arm A: Basimglurant/NOE-101 Experimental Treatment 1 Intervention

* Period 1 (Run-in: Baseline1 to Week 8): Basimglurant once daily dosing starting dose 1.5mg * Period 2 (Double blind: Weeks 9 to 20): Participants will receive double-blind treatment with Basimglurant once daily. * Open-label Extension (OLE): On completion of Period 2, participants will be offered open label treatment with Basimglurant in an open label extension for up to 52 weeks.

Group II: Arm B: Placebo Placebo Group 1 Intervention

- Period 2 (Double blind: Week 9 to Week 20): Participant randomized to placebo will receive the corresponding number of matching placebo capsules.

Who Is Running the Clinical Trial?

Noema Pharma AG

Lead Sponsor

Trials

6

Recruited

570+

Findings from Research

Mavoglurant, a drug targeting metabotropic glutamate receptor subtype-5, was found to be well tolerated in a long-term study with 267 participants (119 adolescents and 148 adults) over up to 34 months, showing no new safety concerns.

While the drug did not show significant behavioral benefits in initial studies, gradual improvements were noted in the open-label extensions, suggesting that further research is needed to explore its efficacy in treating Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents. Hagerman, R., Jacquemont, S., Berry-Kravis, E., et al.[2019]

Basimglurant (compound 2) is a potent negative allosteric modulator of mGlu5 that shows similar efficacy to diazepam in anxiety tests but requires significantly lower doses, indicating its potential as a safer alternative for treating anxiety and depression.

CTEP (compound 3) is the first mGlu5 NAM with a long half-life in rodents, making it suitable for chronic studies, which could help in understanding its long-term effects and therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases. Jaeschke, G., Kolczewski, S., Spooren, W., et al.[2015]

Carbamazepine is the primary treatment for trigeminal neuralgia, showing significant efficacy with a number needed to treat (NNT) of 1.7 for at least 50% pain relief, making it a highly effective option.

Other medications like baclofen and lamotrigine also provide pain relief, with baclofen having an NNT of 1.4, while lamotrigine can enhance relief for patients not fully helped by carbamazepine or phenytoin (NNT = 2.1).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of trigeminal neuralgia. Sindrup, SH., Jensen, TS.[2019]

Mirogabalin, a medication that targets specific calcium channels, showed promising effectiveness in relieving trigeminal neuropathy symptoms in two postoperative cases after skull base surgery, with one patient experiencing immediate improvement.

These findings suggest that mirogabalin could be a beneficial option for managing postoperative neuropathic pain, but further research with larger patient groups is needed to validate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Mirogabalin Besylate for Trigeminal Neuropathy after Skull Base Surgery: Illustrative Cases. Karatsu, K., Tamura, R., Miyauchi, T., et al.[2023]

Carbamazepine is the first-line treatment for trigeminal neuralgia, but if patients cannot tolerate it, alternative medications like phenytoin, baclofen, and clonazepam can be considered, although their relative effectiveness is not well established.

For patients who do not respond to medication, surgical options like microvascular decompression are recommended for younger patients, while older patients may benefit from radiofrequency thermal rhizotomy, with other techniques available if initial treatments fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trigeminal Neuralgia. Perkin, GD.[2020]

References

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

Effect of the mGluR5-NAM Basimglurant on Behavior in Adolescents and Adults with Fragile X Syndrome in a Randomized, Double-Blind, Placebo-Controlled Trial: FragXis Phase 2 Results. [2018]

2. England pubmed.ncbi.nlm.nih.gov

A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans. [2017]

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

Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. [2015]

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

Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents. [2019]

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

Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases. [2015]

6. England pubmed.ncbi.nlm.nih.gov

The α6 subunit-containing GABAA receptor: A novel drug target for inhibition of trigeminal activation. [2021]

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

Pharmacotherapy of trigeminal neuralgia. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of Mirogabalin Besylate for Trigeminal Neuropathy after Skull Base Surgery: Illustrative Cases. [2023]

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

Trigeminal Neuralgia. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Assessment of efficacy and safety of eslicarbazepine acetate for the treatment of trigeminal neuralgia. [2019]