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

Trigeminal Neuralgia Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05217628
• Other study ID #: NOE-TGN-201
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 11, 2022
• Est. completion date: January 31, 2026

Study information

• Verified date: April 2024
• Source: Noema Pharma AG
• Contact: Noema Pharma
• Phone: Please contact via email:
• Email: clinicaltrials[@]noemapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 31, 2026
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ICHD3 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 (Diagnostic and Statistical Manual for Mental Disorders, 5th edition) 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 ICHD3 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.

Related Conditions & MeSH terms

• Neuralgia
• Trigeminal Neuralgia

Intervention

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:
• Placebo
Participant randomized to receive matching placebo once daily.

Locations

Country	Name	City	State
Denmark	Danish Headache Center (Site #: 1201)	Copenhagen
Germany	Universitätsklinikum Bonn (Site #: 1707)	Bonn
Germany	Universitätsklinikum Essen (Site #: 1702)	Essen	Nordrhein-Westfalen
Germany	Kopfschmerzzentrum Frankfurt (Site #: 1706)	Frankfurt am Main	Hessen
Germany	St. Ansgar Krankenhaus Höxter -Klinikum Weser Egge (Site #: 1701)	Höxter
Italy	Azienda Ospedaliera Universitaria Careggi (Site #: 1806)	Florence
Italy	Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta (Site #: 1804)	Milano
Italy	IRCCS San Raffaele Pisana (Site #: 1801)	Roma	Lazio
Italy	La Sapienza-Università di Roma-Policlinico Umberto I (Site #: 1802)	Roma	Lazio
Italy	Università Campus Bio Medico Di Roma (Site #: 1805)	Roma	Lazio
Poland	Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) Zespo (Site #: 2602)	Dabrowa Górnicza
Poland	Centrum Medyczne Linden (Site #: 2605)	Kraków
Poland	FutureMeds - Lodzi - PPDS (Site #: 2606)	Lódz
Poland	Prywatny Gabinet Lekarski U. Chyrchel-Paszkiewicz (Site #: 2604)	Lublin
Poland	MIGRE Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak (Site #: 2601)	Wroclaw
Spain	Hospital Universitario Fundacion Jimenez Diaz (Site #: 1903)	Madrid
Spain	Hospital Universitario La Paz - PPDS (Site #: 1907)	Madrid
Spain	Hospital Universitario Virgen del Rocio - PPDS (Site #: 1904)	Sevilla
Spain	Hospital Clinico Universitario de Valencia (Site #: 1906)	Valencia
Turkey	Afyon Kocatepe University Faculty of Medicine (Site #: 9005)	Afyonkarahisar
Turkey	Uludag University Faculty of Medicine Hospital (Site #: 9001)	Bursa
Turkey	Duzce University Health Application and Research Center (9008)	Düzce
Turkey	Bagcilar Medipol Mega University Hospital (Site #: 9002)	Istanbul
Turkey	Istanbul University Istanbul Medical Faculty Hospital (Site #: 9003)	Istanbul
Turkey	Kocaeli University Faculty of Medicine Hospital (Site #: 9004)	Kocaeli
Turkey	Mersin University Faculty of Medicine Hospital (Site #: 9007)	Mersin
Turkey	Selcuk University Medical Faculty (Site #: 9006)	Selçuklu	Konya
United Kingdom	St Pancras Clinical Research (Site #: 2503)	London	Middlesex
United Kingdom	St. Thomas' Hospital (Site #: 2504)	London
United States	Beth Israel Deaconess Medical Center (Site #: 1004)	Boston	Massachusetts
United States	University of Cincinnati (Site #: 1007)	Cincinnati	Ohio
United States	Kaizen Brain Center (Site #: 1001)	La Jolla	California
United States	Columbia University - Irving Medical Center (Site #: 1008)	New York	New York
United States	University of South Florida (Site #: 1002)	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Noema Pharma AG

Countries where clinical trial is conducted

United States,  Denmark,  Germany,  Italy,  Poland,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Period 2: The impact of pain on general activities of daily living captured in patient diary cards.		12 weeks
Primary	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
Primary	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
Primary	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	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
Secondary	Period 2: Frequency of attacks (paroxysms).	Impact on facial pain measured by patient rated scale via Penn-FPS-R	12 weeks
Secondary	Period 2: Severity of attacks (paroxysms).	Impact on facial pain measured by patient rated scale via Penn-FPS-R	12 weeks
Secondary	Period 2: Severity of continuous pain.	Impact on facial pain measured by patient rated scale via Penn-FPS-R	12 weeks
Secondary	Period 2: Duration of continuous pain.	Impact on facial pain measured by patient rated scale via Penn-FPS-R	12 weeks
Secondary	Period 2: Change in Patient Global Impression of Change (P-GIC).	Impact on facial pain.	12 weeks
Secondary	Period 2: Change in Medication Satisfaction Questionnaire (MSQ).	Impact on facial pain.	12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Open Label Extension: Measure Global Impression of Severity as captured by PGI-S.	Evaluate the continued efficacy of basimglurant on facial pain.	52 weeks