An Efficacy and Safety Study of Basimglurant (NOE-101) in Patients With Trigeminal Neuralgia.

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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Trigeminal Neuralgia
• Intervention / Treatment: Drug: Basimglurant; Other: Placebo

Detailed Description

This study is designed to evaluate the efficacy and safety of basimglurant (NOE-101) 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.

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Glostrup Municipality, Denmark, 2100
    • Danish Headache Center (Site #: 1201)
• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn (Site #: 1707)
• Italy
  • Florence, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi (Site #: 1806)
  • Milan, Italy, 20133
    • Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta (Site #: 1804)
  • Lazio
    • Rome, Lazio, Italy, 00128
      • Università Campus Bio Medico Di Roma (Site #: 1805)
    • Rome, Lazio, Italy, 00163
      • IRCCS San Raffaele Pisana (Site #: 1801)
    • Rome, Lazio, Italy, 00185
      • La Sapienza-Università di Roma-Policlinico Umberto I (Site #: 1802)
• Poland
  • Dąbrowa Górnicza, Poland, 41-300
    • Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) Zespo (Site #: 2602)
  • Krakow, Poland, 30-721
    • Centrum Medyczne Linden (Site #: 2605)
  • Lodz, Poland, 91-363
    • FutureMeds - Lodzi - PPDS (Site #: 2606)
  • Lublin, Poland, 20-090
    • Prywatny Gabinet Lekarski U. Chyrchel-Paszkiewicz (Site #: 2604)
  • Wroclaw, Poland, 52-210
    • MIGRE Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak (Site #: 2601)
• Spain
  • Madrid
    • Madrid, Madrid, Spain, 28040
      • Hospital Universitario Fundacion Jimenez Diaz (Site #: 1903)
    • Madrid, Madrid, Spain, 28046
      • Hospital Universitario La Paz - PPDS (Site #: 1907)
  • Sevilla
    • Seville, Sevilla, Spain, 41013
      • Hospital Universitario Virgen del Rocio - PPDS (Site #: 1904)
  • Valencia
    • Valencia, Valencia, Spain, 46010
      • Hospital Clinico Universitario de Valencia (Site #: 1906)
• Turkey (Türkiye)
  • Afyonkarahisar, Turkey (Türkiye), 03030
    • Afyon Kocatepe University Faculty of Medicine (Site #: 9005)
  • Bursa, Turkey (Türkiye), 16059
    • Uludag University Faculty of Medicine Hospital (Site #: 9001)
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul University Istanbul Medical Faculty Hospital (Site #: 9003)
  • Istanbul, Turkey (Türkiye), 34214
    • Bagcilar Medipol Mega University Hospital (Site #: 9002)
  • Kocaeli, Turkey (Türkiye), 41001
    • Kocaeli University Faculty of Medicine Hospital (Site #: 9004)
  • Mersin, Turkey (Türkiye), 33343
    • Mersin University Faculty of Medicine Hospital (Site #: 9007)
  • Düzce
    • Düzce, Düzce, Turkey (Türkiye), 81620
      • Duzce University Health Application and Research Center (9008)
  • Konya
    • Selçuklu, Konya, Turkey (Türkiye), 42075
      • Selcuk University Medical Faculty (Site #: 9006)
• United Kingdom
  • London
    • London, London, United Kingdom, SE1 7EH
      • St. Thomas' Hospital (Site #: 2504)
  • Middlesex
    • London, Middlesex, United Kingdom, EC2Y 8EA
      • St Pancras Clinical Research (Site #: 2503)
• United States
  • California
    • La Jolla, California, United States, 92037
      • Kaizen Brain Center (Site #: 1001)
  • Florida
    • Miami, Florida, United States, 33142-3911
      • L & A Morales Healthcare INC (Site#: 1011)
    • Tampa, Florida, United States, 33612
      • University of South Florida (Site #: 1002)
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Vista Clinical Research,LLC (Site#: 1010)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (Site #: 1004)
  • Nevada
    • Las Vegas, Nevada, United States, 89102-1972
      • Altea Research - Nevada - ClinEdge - PPDS (Site #1006)
  • New York
    • New York, New York, United States, 10032
      • Columbia University - Irving Medical Center (Site #: 1008)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati (Site #: 1007)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Summary):

1. Ability and willingness to provide written informed consent and to comply with the study procedures.
2. Fluency in the language of the investigator, study staff and the informed consent.
3. Age 18-75 years.
4. Diagnosis of primary trigeminal neuralgia (TN) as per the ICHD-3 criteria confirmed by the study neurologist.
5. 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.
6. 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:

1. Current or prior history of any major psychiatric diagnoses unrelated to TN. Patients with TN-related depressive symptoms are permitted.
2. Current or prior history of mania, or psychotic episodes.
3. History of DSM-5-defined substance dependence and/or substance abuse in the last six months [180 days], except for nicotine.
4. Patient not willing to discontinue their current TN analgesic medication.
5. Use of opioids, except for pain control on a prn basis as long as it does not exceed 2 days per week.
6. Known allergic reaction to the investigational drug or one of its components.

7. Patients with secondary TN as per the ICHD-3 criteria.

   Medication history:

8. Previous treatment with basimglurant, except with the prior agreement of the medical monitor.
9. Treatment with antipsychotics within six months (180 days) of screening.

10. Any investigational drug within 90 days prior to initiation of study drug.

    Medical status:

11. 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.
12. 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.
13. Body mass index > 39kg/m²
14. Patients with moderate or severely impaired hepatic function, ie, Pugh-Child score C.
15. Patients with severe renal impairment, ie, eGFR or creatinine clearance lower than 30mL/min.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm B: Placebo; - Period 2 (Double blind: Week 9 to Week 20): Participant randomized to placebo will receive the corresponding number of matching placebo capsules.	Other: Placebo; Participant randomized to receive matching placebo once daily.
Experimental: Arm A: Basimglurant/NOE-101; 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; 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.; Other Names: NOE-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Period 1: Mean change from Period 1 baseline (BL1) to Week 8 in the total patient-rated Penn-Facial Pain Scale-Revised (Penn-FPS-R) scale.	Evaluate 8-week once daily basimglurant on pain associated with TN on the following: Impact on Facial Pain; Patient perceived change of the pain; Pain assessments; Pain freedom; Patient medication satisfaction	8 weeks
Period 1: Measure Global Impression of change from Period 1 baseline (BL1) to Week 8.	Evaluate 8-week once daily basimglurant on pain associated with TN on the following: Impact on Facial Pain; Patient perceived change of the pain; Pain assessments; Pain freedom; Patient medication satisfaction	8 weeks
Period 1: Number and severity of attacks (paroxysms).	Evaluate 8-week once daily basimglurant on pain associated with TN on the following: Impact on Facial Pain; Patient perceived change of the pain; Pain assessments; Pain freedom; Patient medication satisfaction	8 weeks
Period 1: Duration of continuous pain compared with BL1.	Evaluate 8-week once daily basimglurant on pain associated with TN on the following as measured by patient rated scale via Penn-FPS-R: Impact on Facial Pain; Patient perceived change of the pain; Pain assessments; Pain freedom; Patient medication satisfaction	8 weeks
Period 1: Severity of continuous pain compared with BL1.	Evaluate 8-week once daily basimglurant on pain associated with TN on the following as measured by patient rated scale via Penn-FPS-R: Impact on Facial Pain; Patient perceived change of the pain; Pain assessments; Pain freedom; Patient medication satisfaction	8 weeks
Period 1: Number of pain free days.	Evaluate 8-week once daily basimglurant on pain associated with TN on the following: Impact on Facial Pain; Patient perceived change of the pain; Pain assessments; Pain freedom; Patient medication satisfaction	8 weeks
Period 1: Patient reported rating of the Medication Satisfaction Questionnaire (MSQ).	Evaluate 8-week once daily basimglurant on pain associated with TN on the following: Impact on Facial Pain; Patient perceived change of the pain; Pain assessments; Pain freedom; Patient medication satisfaction	8 weeks
Period 2: The impact of pain on general activities of daily living captured in patient diary cards.		12 weeks

Collaborators and Investigators

• Sponsor: Noema Pharma AG

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Estimated): February 2, 2027
• Study Completion (Estimated): April 24, 2027

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Nervous System Diseases; Cranial Nerve Diseases; Trigeminal Nerve Diseases; Facial Neuralgia; Facial Nerve Diseases; Trigeminal Neuralgia; 2-chloro-4-(1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl)pyridine
• Other Study ID Numbers: NOE-TGN-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No