Efficacy and Safety Evaluation of N-[4-[2-[4-(3-Cyanophenyl)Piperazin-1-yl]Ethyl]Cyclohexyl]-3-Methoxypropanamide in Adults with Essential Tremor
- Trial ID
- 2024-517987-46-00
- Protocol
- P23-05
- Sponsor
- Bioprojet Pharma
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicentre, randomised, double-blind, placebo-controlled, parallel-group trial is to evaluate the **efficacy** of BP1.4979 in treating **essential tremor**. This objective is clinically relevant as essential tremor is a common movement disorder that can significantly impact patients' quality of life, and effective treatment options are limited.
Secondary objectives include:
- Assessing the effect of BP1.4979 on functional disability associated with essential tremor.
- Evaluating the impact of BP1.4979 on patient-reported quality of life.
- Assessing the safety and tolerability of BP1.4979.
Participants
The clinical trial focuses on evaluating the efficacy of BP1.4979 in treating **Essential Tremor**. The study population includes both male and female participants aged between 18 and 85 years. Participants are required to have a confirmed diagnosis of Essential Tremor, characterized by a bilateral upper limb action tremor with a minimum duration of three years. The trial includes individuals who have not undergone previous surgical procedures for tremor treatment and those who have maintained a consistent dose of anti-tremor medication for at least four weeks prior to screening. Participants must not exhibit significant imbalance due to tremors or have an increased risk of falls. The trial population was selected based on specific inclusion criteria, including the ability to comply with trial requirements and procedures. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group study to evaluate the efficacy and safety of BP1.4979 in adult patients with **essential tremor**. The trial is set to commence recruitment on June 2, 2025, and is estimated to conclude by December 1, 2026. Participants will be involved in the study for a maximum treatment period of 32 weeks, during which they will receive the investigational product in the form of a tablet, administered orally. The primary objective is to assess the change in the total score of the Performance Subscale of The Essential Tremor Rating Assessment Scale (TETRAS-P) after 4 weeks of treatment.
The trial will begin with a screening visit to confirm eligibility based on specific inclusion criteria, such as age between 18-85 years, a confirmed diagnosis of essential tremor, and a stable dose of any anti-tremor medication for at least four weeks prior to screening. Participants must also provide written informed consent. Following the screening, eligible participants will be randomized to receive either the investigational product or a placebo. The study will include regular follow-up visits to monitor safety and efficacy, with assessments conducted using the TETRAS-P scale. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted.
Participants are expected to comply with all trial requirements, including maintaining their current medication dosage and not using prohibited concomitant medications. Conditions that may lead to early termination from the study include non-compliance with trial procedures, significant adverse events, or withdrawal of consent. The trial does not plan for any secondary endpoints, focusing solely on the primary efficacy endpoint. The investigational product, BP1.4979, is a chemical compound with a maximum daily dose of 40 mg and a total dose limit of 1280 mg over the treatment period.
Treatment
The clinical trial involves the evaluation of **BP1.4979**, an experimental medication, in adult patients with **essential tremor**. The active substance in BP1.4979 is **N-[4-[2-[4-(3-cyanophenyl)piperazin-1-yl]ethyl]cyclohexyl]-3-methoxypropanamide**, a chemical compound. The pharmaceutical form of BP1.4979 is a tablet, and it is administered orally. The maximum daily dose is 40 mg, with a total maximum dose of 1280 mg over a treatment period of up to 32 days. The medication is not formulated for pediatric use and is not classified as an orphan drug. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
In addition to the experimental treatment, the study includes a **placebo** as a comparator. The placebo is designed to match the test product in appearance but does not contain the active substance. The use of a placebo allows for a double-blind, placebo-controlled trial design, ensuring that neither the participants nor the investigators know which treatment is being administered, thereby reducing bias in the assessment of the medication's efficacy and safety.
Efficacy
The efficacy of BP1.4979 in treating **Essential Tremor** will be assessed in a multicentre, randomised, double-blind, placebo-controlled, parallel-group trial. The primary efficacy endpoint is defined as the change in the total score of the Performance Subscale of The Essential Tremor Rating Assessment Scale (TETRAS-P) after 4 weeks of treatment. This scale is a validated tool used to measure the severity of tremor symptoms in patients with Essential Tremor.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent obtained prior to any trial-related procedures.
- Male or female ≥18-85 years old.
- 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.
- 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.
- 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.
- The patient should not have undergone any previous surgical procedures specifically for tremor treatment.
- There should be a minimum interval of four (4) months between the patient’s last botulinum injection and the screening.
- The patient should not exhibit significant imbalance due to the tremors or have an increased risk of falls.
- 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).
- 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.
- If required, patient must be insured by appropriate national health insurance system (mandatory for France).
Exclusion Criteria
- 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.
- Isolated head tremor not accompanied with tremor of any other body part.
- 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).
- 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.
- Patient who may have had direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
- Patient who takes concomitant treatment with more than three drugs to treat ET.
- 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.
- 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.
- 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.
- Female patient: pregnant or lactating woman. [Pregnancy is confirmed by a positive serum human chorionic gonadotrophin laboratory test (> 5mIU/mL)].
- 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.
- 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.
- 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.
- Patient with concomitant prolactin-dependent tumour (e.g., pituitary tumour or breast cancer)
- 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.
- 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.
- 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.
- History of hypersensitivity to any of the study drug constituents.
- Current or recent history (less than one year) of alcohol or drug abuse.
- 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).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 02 Jun 2025 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Matches test product | Placebo | N/A | — | — | — | N/A |