Basimglurant for Trigeminal Neuralgia

Recruiting at 28 trial locations

Overseen By Noema Pharma

Age: 18+

Sex: Male

Travel: May Be Covered

Trial Phase: Phase 2 & 3

Sponsor: Noema Pharma AG

Must not be taking: Opioids, Antipsychotics

Disqualifiers: Major psychiatric, Substance abuse, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

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}

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.

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

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

In a 12-week study involving 183 participants with Fragile X syndrome, the mGluR5 negative allosteric modulator basimglurant did not show significant improvement in behavioral symptoms compared to placebo, particularly at the 0.5 mg dose.

While basimglurant was generally well-tolerated, there was a higher incidence of psychiatric adverse events, including hallucinations, suggesting careful consideration of safety in future trials.

NCBI (Pubmed)

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. Youssef, EA., Berry-Kravis, E., Czech, C., et al.[2018]

The study found that the novel mGlu5 receptor antagonist, basimglurant, has an oral bioavailability of approximately 67%, indicating that a significant portion of the drug is effectively absorbed into the bloodstream after oral administration.

Using a double-tracer technique, the research revealed that basimglurant is primarily excreted through urine as metabolites, with a long terminal half-life of 178 hours for the drug's radioactivity, suggesting prolonged effects in the body.

NCBI (Pubmed)

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. Guerini, E., Schadt, S., Greig, G., et al.[2017]

Basimglurant is a novel mGlu5 negative allosteric modulator showing promising antidepressant-like properties in preclinical studies, with a favorable pharmacological profile that supports its potential use in treating major depressive disorder (MDD).

The drug demonstrates good oral bioavailability, a long half-life for once-daily dosing, and has shown effects on anxiety and pain, suggesting it may also help with common comorbidities associated with MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. Lindemann, L., Porter, RH., Scharf, SH., et al.[2015]

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]

The study identifies α6 subunit-containing GABAA receptors (α6GABAARs) in trigeminal ganglia as a promising target for migraine treatment, showing that their activation can reduce trigeminal vascular system (TGVS) activation in an animal model of migraine.

Using a selective positive allosteric modulator (PAM) for α6GABAARs, Compound 6, significantly decreased neuronal activation and related migraine markers, suggesting that α6GABAAR-selective PAMs could be developed into effective new migraine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The α6 subunit-containing GABAA receptor: A novel drug target for inhibition of trigeminal activation. Fan, PC., Lai, TH., Hor, CC., et al.[2021]

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]

In a study of 18 patients with trigeminal neuralgia, treatment with eslicarbazepine acetate significantly reduced pain intensity from a median score of 9.5 to 2.5 and decreased the frequency of pain episodes from 70 per week to just 0.37, indicating strong efficacy.

Despite some adverse events reported by 61% of patients, 88.9% reported good tolerance to eslicarbazepine, suggesting it is a safe and well-tolerated option for managing trigeminal neuralgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of efficacy and safety of eslicarbazepine acetate for the treatment of trigeminal neuralgia. Sanchez-Larsen, A., Sopelana, D., Diaz-Maroto, I., et al.[2019]

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]