N-[4-[2-[4-(3-CYANOPHENYL)PIPERAZIN-1-YL]ETHYL]CYCLOHEXYL]-3-METHOXYPROPANAMIDE for Essential tremor

Inclusion criteria

• {"criterion_text":"- Written informed consent obtained prior to any trial-related procedures.\n- Female patient: post-menopausal woman having at least 12 months of natural (spontaneous) amenorrhea without any alternative medical cause, or women of childbearing potential (WOCBP, defined as all fertile woman, following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) using a highly effective method of contraception for the duration of the trial and for one (1) month after stopping the investigational medication.\n- If required, patient must be insured by appropriate national health insurance system (mandatory for France).\n- Male or female ≥18-85 years old.\n- Confirmed diagnosis of ET, characterized by meeting the following criteria: (a) the presence of a bilateral upper limb action tremor that occurs in isolation; (b) a minimum duration of three (3) years; and (c) the tremor may or may not be present in other areas such as the voice, or lower limbs.\n- Patient with ET, characterized by a TETRAS-P score of at least 1.5 in either the forward posture, wing beating posture, or finger-to-nose movement of at least one upper extremity. This assessment will be conducted using the Performance subscale of The Essential Tremor Rating Assessment Scale, following the criteria established by the Tremor Investigation Group.\n- If taking anti-tremor medication(s), patient must have been on a consistent and unchanged dose of anti-tremor medication for at least four (4) weeks prior to the screening. Additionally, she/he must be willing to maintain their current medication dosage throughout the entire duration of the study.\n- The patient should not have undergone any previous surgical procedures specifically for tremor treatment.\n- There should be a minimum interval of four (4) months between the patient’s last botulinum injection and the screening.\n- The patient should not exhibit significant imbalance due to the tremors or have an increased risk of falls.\n- Patient must have a cooperative attitude and be able to comply with the entire trial requirements and procedures (e.g., trial-related questionnaire, drug compliance, not use prohibited concomitant medications)."}

Exclusion criteria

• {"criterion_text":"- Severe tremor, defined as patient with ET characterized by a TETRAS-P score of ≥ 3 in either the forward posture, wing beating posture, or finger-to-nose movement of at least one upper extremity, or tremor of trunk.\n- Female patient: pregnant or lactating woman. [Pregnancy is confirmed by a positive serum human chorionic gonadotrophin laboratory test (> 5mIU/mL)].\n- History of significant cardiovascular disease, particularly recent history of myocardial infarction or unstable coronary artery disease, arrhythmias, congestive heart failure, uncontrolled arterial hypertension. Patient with a known history of long QT syndrome with or without history of syncope.\n- Patient with a clinically significant deviation(s) from normal on 12-lead ECG that results in an active medical problem, as determined by the Investigator at screening or has a corrected QT interval using Fridericia’s formula (QTcF) ≥450 msec for males or ≥470 msec for females.\n- Patient with unstable or uncontrolled disease that might affect the patient’s safety and/or interfere with the conduct of the study according to the Investigator’s judgement.\n- Patient with concomitant prolactin-dependent tumour (e.g., pituitary tumour or breast cancer)\n- Patient with history of malignancy within the past 5 years with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.\n- Established diagnosis of human immunodeficiency virus (HIV), hepatitis B viral infection or is positive for hepatitis surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) at screening or established diagnosis of hepatitis C viral infection or is positive for hepatitis C antibody at screening.\n- Patient who has a laboratory abnormality at screening as follows: ALT, AST values > 2 x upper limit of normal (ULN), Serum creatinine value >1.5 x ULN, GFR < 50 ml/min/1.73m2 (CKD-EPI formula), Absolute neutrophils count <1.0x109 /L, Platelets < 100x109 /L or who has any other uncontrolled clinically significant laboratory abnormalities that would affect interpretation of the study data or the patient’s participation in the study.\n- History of hypersensitivity to any of the study drug constituents.\n- Current or recent history (less than one year) of alcohol or drug abuse.\n- Isolated head tremor not accompanied with tremor of any other body part.\n- Patient having received any other investigational drug within the preceding 30 days, or a longer and more appropriate time as determined by the Investigator (e.g., approximately five half-lives of the previous investigational drug).\n- Patient who has a medical history or clinical evidence of any other conditions, whether medical, neurological, or psychiatric, that could potentially explain or contribute to the presence of tremors. Examples of such conditions include but are not limited to Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, cerebellar disease (including spinocerebellar ataxias), primary dystonia, Fragile X Tremor/Ataxia syndrome or a family history of Fragile X syndrome, traumatic brain injury, psychogenic tremor, alcohol or benzodiazepine abuse or withdrawal, multiple sclerosis, polyneuropathy, endocrine disorders such as hyperthyroidism or unstable treatment of hypothyroidism, food-induced tremors, or tremors related to the use of supplements (e.g., tremors caused by beta agonists or caffeine).\n- Patient who takes a medication which may induce tremor. For reference, some of the common medications and substances which may potentially cause physiologic tremors are: Amiodarone, certain antidepressants (e.g., serotonin reuptake inhibitors, serotonin-noradrenaline reuptake inhibitors, tricyclic antidepressants), antiseizure medications such as bromides carbamazepine, lacosamide, lamotrigine, phenytoin, valproic acid, certain beta-agonists such as albuterol and terbutaline, certain glucocorticoids such as dexamethasone or prednisone, the mood stabilizer lithium, sympathomimetics such as amphetamine salts, epinephrine, methylphenidate, thyroid hormone replacement therapies such as levothyroxine, substances such as caffeine, cocaine and nicotine, and certain other treatments such as cyclosporine, tacrolimus, theophylline.\n- Patient who may have had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.\n- Patient who takes concomitant treatment with more than three drugs to treat ET.\n- Patient who has undergone any prior procedures for the treatment of ET such as deep brain stimulation, brain lesioning, or magnetic resonance (MR)-guided procedures, including MR-guided focused ultrasound.\n- Patient who has a historical or clinical evidence of tremor with a psychogenic origin, which includes conditions like eating disorders or major depression, among others.\n- Patient with a history of suicidal behaviour within the past two years or who is currently assessed to be at risk for suicide as assessed by the C-SSRS score of “YES” on questions 4 or 5, and/or based on clinical evaluation by the investigator, is not eligible for the study."}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint is the change in the total score of the Performance Subscale of The Essential Tremor Rating Assessment Scale (TETRAS-P) after 4 weeks of treatment.","definition_or_measurement_approach":"Change in total score of the Performance Subscale of TETRAS-P measured after 4 weeks of treatment (Performance subscale assessment per Tremor Investigation Group criteria)."}

Secondary endpoints

• {"endpoint_text":"- No secondary endpoints are planned in this trial.","definition_or_measurement_approach":""}

Methods

• Recruitment materials documented: Posters (K2_Recruitment Materials_Poster 1-4) associated with the France Part II (associatedEntityId 213868).
• Flyer text (K2_Recruitment Materials_Flyer text) — recruitment material file present (France).
• K1_Recruitment arrangements (document titled "K1_Recruitment arrangements") available (France).

France

Earliest CTIS Part Ii Submission Date

03-06-2025

Latest Decision Or Authorization Date

13-06-2025

Processing Time Days

10

Number Of Sites

14

Number Of Participants

50

Primary sponsor

Full Name

Bioprojet Pharma

Organisation Type

Pharmaceutical company

Country Of Registered Address

France