An Efficacy and Safety Study of Basimglurant in Patients With Trigeminal Neuralgia.

Study Overview
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Brief Summary
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Trigeminal neuralgia (TN), also called tic douloureux, is the most common form of craniofacial neuropathic pain and is considered the cause of one of the most painful afflictions known in medical practice. This study is designed to evaluate the efficacy and safety of 1.5mg - 3.5mg basimglurant in adults with TN.

Detailed Description
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This study is designed to evaluate the efficacy and safety of basimglurant in patients with TN. Basimglurant is a potent inhibitor of metabotropic glutamate receptor 5 (mGluR5) which controls a wide range of processes in both central and peripheral nervous system. Inhibition of the mGluR5 receptor has shown therapeutic potential for pain associated with conditions such as TN. The drug has been shown to have a favorable safety profile in adults, children and adolescents. The aim of the study is to determine whether Basimglurant decreases both duration and intensity of facial pain associated with TN by use of a patient pain diary and the Patient-reported Global Impression of Change (PGI-C) compared to baseline.

Official Title
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A Phase II/III, Multicentre, 8-week run-in Phase Followed by a 12-week, Prospective, Parallel-group, Double-blind, Randomized Withdrawal, Placebo-controlled Study, With a 52 Week Open Label Extension, to Evaluate the Efficacy and Safety of Daily 1.5 to 3.5 mg Basimglurant in Patients With Pain Associated With Trigeminal Neuralgia With Suboptimal Response to Their Current Anti-pain Therapy.

Conditions
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Trigeminal Neuralgia

Intervention / Treatment
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* Drug: Basimglurant
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Summary): Ability and willingness to provide written informed consent and to comply with the study procedures. Fluency in the language of the investigator, study staff and the informed consent. Age 18-75 years. Diagnosis of primary trigeminal neuralgia (TN) as per the ICHD3 criteria confirmed by the study neurologist. Experience pain due to TN and at baseline, experience at least 3 paroxysms per day of at least intensity of 4 or more on a pain intensity numerical rating scale (PI-NRS) during the last 7 days. Female patients who are either sterile or menopausal. For female patients with childbearing potential, must be neither pregnant nor lactating (with appropriate contraceptive precautions and prior negative pregnancy tests). Exclusion Criteria (Summary): Patients who meet any of the following criteria will be excluded from participation in this study: Current or prior history of any major psychiatric diagnoses unrelated to TN. Patients with TN-related depressive symptoms are permitted. Current or prior history of mania, or psychotic episodes. History of DSM-5-defined substance dependence (Diagnostic and Statistical Manual for Mental Disorders, 5th edition) and/or substance abuse in the last six months [180 days], except for nicotine. Patient not willing to discontinue their current TN analgesic medication. Use of opioids, except for pain control on a prn basis as long as it does not exceed 2 days per week. Known allergic reaction to the investigational drug or one of its components. Patients with secondary TN as per the ICHD3 criteria. Medication history: Previous treatment with basimglurant, except with the prior agreement of the medical monitor. Treatment with antipsychotics within six months (180 days) of screening. Any investigational drug within 90 days prior to initiation of study drug. Medical status: Evidence of clinically significant, uncontrolled, unstable medical conditions or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke or transient ischemic attack during the 6 months prior to screening. Subject has a history of gastric, or small intestinal surgery (including gastric bypass, gastric banding, gastric sleeve, gastric balloon, etc.) that may, in the opinion of the investigator, may cause malabsorption, or has a disease of the GI tract that causes malabsorption. Body mass index > 39kg/m² Patients with moderate or severely impaired hepatic function, ie, Pugh-Child score C. Patients with severe renal impairment, ie, eGFR or creatinine clearance lower than 30mL/min.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Basimglurant<br>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. | Drug: Basimglurant<br>* Period 1: Basimglurant 1.5 to 3.5 mg QD titrated on individual tolerability. Period 2: Patients randomized to receive either double blind Basimglurant at the tolerated dose from Period 1 or Placebo. OLE: Open label Basimglurant at the dose tolerated from Period 2, patients previously assigned placebo in period to be titrated to the Period 1.<br>|
| Placebo Comparator: Arm B: Placebo<br>- Period 2 (Double blind: Week 9 to Week 20): Participant randomized to placebo will receive the corresponding number of matching placebo capsules. | Other: Placebo<br>* Participant randomized to receive matching placebo once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Period 1: Incidence and severity of adverse events, laboratory, vital signs and cardiovascular events. | Change in pain as measured by the pain diary (TnED). | 8 weeks | 
| Period 2: Time to Loss of Efficacy or pain recurrence defined as the confirmed increase in the number of weekly paroxysms or re-emergence of continuous pain and/or the need for rescue medication. | To assess the maintenance of effect on pain. | 12 weeks | 
| Open Label Extension: Incidence and severity of adverse events, laboratory, vital signs and cardiovascular events. | To evaluate the long-term safety of basimglurant daily dosing. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Period 2: Mean change in the total patient-rated Penn-Facial Pain Scale-Revised (Penn-FPS-R) scale compared with Period 2 baseline (BL2). | Impact on facial pain. | 12 weeks | 
| Period 2: Frequency of attacks (paroxysms). | Impact on facial pain measured by patient rated scale via Penn-FPS-R | 12 weeks | 
| Period 2: Severity of attacks (paroxysms). | Impact on facial pain measured by patient rated scale via Penn-FPS-R | 12 weeks | 
| Period 2: Severity of continuous pain. | Impact on facial pain measured by patient rated scale via Penn-FPS-R | 12 weeks | 
| Period 2: Duration of continuous pain. | Impact on facial pain measured by patient rated scale via Penn-FPS-R | 12 weeks | 
| Period 2: Change in Patient Global Impression of Change (P-GIC). | Impact on facial pain. | 12 weeks | 
| Period 2: Change in Medication Satisfaction Questionnaire (MSQ). | Impact on facial pain. | 12 weeks | 
| Open Label Extension: Frequency of attacks (paroxysms). | Evaluate the continued efficacy of basimglurant on facial pain measured by patient rated scale via Penn-FPS-R | 52 weeks | 
| Open Label Extension: Severity of attacks (paroxysms). | Evaluate the continued efficacy of basimglurant on facial pain measured by patient rated scale via Penn-FPS-R | 52 weeks | 
| Open Label Extension: Severity and duration of continuous pain reported in patient pain diary. | Evaluate the continued efficacy of basimglurant on facial pain. | 52 weeks | 
| Open Label Extension: Measure Global Impression of Severity as captured by PGI-S. | Evaluate the continued efficacy of basimglurant on facial pain. | 52 weeks |