| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Trigeminal neuralgia is a chronic pain condition affecting the trigeminal nerve in the face causing sudden, severe facial pain. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10044652 |
| E.1.2 | Term | Trigeminal neuralgia |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Period 1: Run-in: To evaluate the safety of basimglurant daily dosing 1.5-3.5 mg
Period 2: Double Blind: To assess the maintenance of effect on pain of double-blind 12-week once daily dosing of basimglurant 1.5–3.5 mg compared with placebo in patients with TN.
Open-Label Extension: To evaluate the long-term safety of basimglurant daily dosing 1.5-3.5 mg. |
|
| E.2.2 | Secondary objectives of the trial |
Period 1: Run-in: To evaluate the efficacy of 8-week once daily treatment with basimglurant on pain associated with trigeminal neuralgia on the following disease aspects:
-Impact on Facial Pain
-Patient perceived change of the pain
-Quantitative and qualitative pain assessments
-Pain freedom
-Patient medication satisfaction
Period 2: Double Blind: To evaluate the effect of double-blind treatment of once daily dose of basimglurant versus placebo on the following disease aspects:
• Impact on facial pain
• Pain frequency and severity
• Patient perceived perception of change in pain
• Patient medication satisfaction
• Safety of basimglurant once daily dosing 1.5-3.5 mg compared with placebo
• The impact of pain on general activities of daily living
Open-Label Extension:
To evaluate the continued efficacy of basimglurant with once daily dosing 1.5-3.5 mg on the following disease aspects:
• Impact on facial pain
• Pain frequency and severity
• Patient perceived severity of pain
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients who meet all entry criteria will be eligible to participate in the study:
At study entry (Period 1), patients must meet all the following criteria:
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 (classical or idiopathic (with or without paroxysms)) trigeminal neuralgia as per the ICHD3 criteria confirmed by the study neurologist:
• Classical TN, purely paroxysmal
• Classical TN with concomitant continuous pain
• Idiopathic TN, purely paroxysmal
• Idiopathic TN with concomitant continuous pain
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 PI-NRS during
the last 7 days.
6. Female patients who are either sterile or menopausal. For female patients with childbearing potential:
A female patient is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
• For women of child bearing potential (WOCBP), female patients should be using an acceptable contraceptive method during the study intervention period (at a minimum until 28 days after the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
• WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 28 days before the first dose of study intervention.
Entry into Period 2
Only patients who meet the treatment response criteria below will be allowed to participate in
Period 2:
1. For patients classified at study entry with paroxysms and concomitant continuous pain, at least 30% decrease in the total number or severity of
paroxysms over the last 7 days of Period 1 as compared to the total number recorded in the last 7 days of screening (BL1) or at least 30% reduction in the mean severity of continuous pain experienced over the last 7 days of Period 1 compared to BL1 or at least 30% reduction in pain interference over the last 7 days of Period 1 compared to BL1.
2. For patients classified at study entry with paroxysms without concomitant continuous pain, at least 30% decrease in the total number
or severity of paroxysms or pain interference over the last 7 days of Period 1 as compared to the total number recorded in the last 7 days of
screening (BL1).
|
|
| E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from participation in this study:
1. Patients who express suicidal ideation or have recent history of suicidal behavior and who, in the opinion of the investigator, are at risk
of harming themselves.
2. Current or prior history of any major psychiatric diagnoses unrelated to TN. Patients with TN-related depressive symptoms are permitted.
3. History of Diagnostic and Statistical Manual for Mental Disorders, 5th edition 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 analgesics.
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.
Patients with secondary TN as per the ICHD3 criteria.
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) prior to screening. Treatment of depressive symptoms with selective serotonin reuptake inhibitors is permitted if started more than 6 weeks prior to 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 severely impaired hepatic function, ie, Child-Pugh
score C.
15. Patients with severe renal impairment, ie, eGFR or creatinine
clearance lower than 30 mL/min.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Period 1: Run-In
-Change in pain as measured by the pain diary (TnED). Incidence and severity of AEs. Laboratory, vital signs and cardiovascular safety will also be evaluated.
Period 2: Double Blind:
--Time to Loss of Efficacy for each participant as determined by the DSMB.
Open-Label Extension (OLE):
-Incidence and severity of adverse events. Laboratory, vital signs and cardiovascular safety will also be evaluated.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
PERIOD 1
Week 1, Day 8
Week 1, Day 8+2
Week 2, Day 15
Week 2, Day 15+2
Week 3, Day 22
Week 3, Day 22+2
Week 4, Day 29
Week 4, Day 29+2
Week 5, Day 36
Week 6, Day 43
Week 7, Day 50
Week 8, Day 57
PERIOD 2
Week 10, Day 71
Week 12, Day 85
Week 14, Day 99
Week 16, Day 113
Week 18, Day 127
Week 20, Day 141 / EoT Period 2
Open Label Extension:
Week 2, 3, 4, 5
Month 3, 6, 9, 12 |
|
| E.5.2 | Secondary end point(s) |
Period 1: Run-In
- Proportion of pain free days as measured by TnED. Proportion and severity of attacks (paroxysms) as well as duration and severity of
continuous pain compared with BL1, as measured by TnED
- Changes in pain interference with daily activities compared to BL1, as measured by TnED
- Mean change from BL1 to Week 8 in the total patient-rated PENN-FPS-R
- PGI-C from BL1 to Week 8
- Patient reported rating of the MSQ.
Period 2: Double Blind:
- Proportion of pain free days as measured by TnED. Proportion and severity of attacks (paroxysms) as well as duration and severity of
continuous pain compared with BL1, as measured by TnED
- Changes in pain interference with daily activities compared to BL1, as measured by TnED
- Mean change in the total patient-rated PENN-FPS-R compared with BL2
- PGI-C as compared with BL2
- Patient reported rating of the MSQ
- Incidence and severity of AEs. Laboratory and cardiovascular safety will also be evaluated.
Open-Label Extension (OLE):
-Proportion of pain free days as measured by TnED. Proportion and severity of attacks (paroxysms) as well as severity and duration of
continuous pain, as measured by TnED
- Pain interference with daily activities, as measured by TnED
- Mean scores in the total patient-rated PENN-FPS-R
- Overall patient global impression measured by the PGI-S |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PERIOD 1
Week 1, Day 8+2
Week 2, Day 15
Week 2, Day 15+2
Week 3, Day 22
Week 3, Day 22+2
Week 4, Day 29
Week 4, Day 29+2
Week 5, Day 36
Week 6, Day 43
Week 7, Day 50
Week 8, Day 57
PERIOD 2
Week 10, Day 71
Week 12, Day 85
Week 14, Day 99
Week 16, Day 113
Week 18, Day 127
Week 20, Day 141 / EoT Period 2
Open Label Extension:
Week 2, 3, 4, 5
Month 3, 6, 9, 12 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| enriched, randomized withdrawal, open label study |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United Kingdom |
| United States |
| Denmark |
| Germany |
| Italy |
| Poland |
| Spain |
| Türkiye |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of study is defined as LSLV or the last scheduled procedure, planned for May 2025 with the addition of new EEA country participation. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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