Efficacy and Safety Evaluation of Suvecaltamide in Treating Moderate to Severe Residual Tremor in Parkinson's Disease: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2024-515177-94-00
- Protocol
- JZP385-202-01
- Sponsor
- Cavion Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of suvecaltamide, administered once daily for 17 weeks, in improving functional and performance-based impairment due to tremor in individuals with moderate to severe residual tremor associated with **Parkinson's Disease**. This is clinically relevant as it aims to address a significant symptom that affects the quality of life in patients with Parkinson's Disease, potentially offering a new therapeutic option.
Secondary objectives include evaluating the safety and tolerability of suvecaltamide when administered under the same conditions. This is crucial for understanding the risk-benefit profile of the treatment, ensuring that any therapeutic benefits are not outweighed by adverse effects.
Participants
The clinical trial involves a total of **79 participants** diagnosed with **Parkinson's Disease**. The study population includes both male and female subjects, aged between **40 to 85 years**. Participants were selected based on specific inclusion criteria, including a diagnosis of clinically probable or established Parkinson's Disease within the past five years, and a body mass index ranging from 17 to 45 kg/m². All participants are required to be on a stable dosing regimen of their Parkinson's Disease medications for at least six weeks prior to screening and must maintain this stability throughout the study. The trial does not include a vulnerable population. Participants are expected to have moderate to severe impairment associated with tremor and must be willing and able to comply with the study design and schedule. Lifestyle considerations such as diet and physical activity are not specified, but participants must be capable of giving informed consent and adhere to contraceptive guidelines if applicable.
Plans and Procedures
The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled, flexible-dosing, parallel-group, multicenter study designed to evaluate the efficacy and safety of **suvecaltamide** in the treatment of moderate to severe residual tremor in participants with **Parkinson's Disease**. The trial will span a total duration of 17 weeks, during which participants will receive the investigational product or placebo. The primary objective is to assess the efficacy of suvecaltamide administered once daily to improve functional and performance-based impairment due to tremor. Secondary endpoints include evaluating the incidence and severity of adverse events, as well as safety laboratory assessments, vital signs, ECG results, and other safety measures.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age, body mass index, and a confirmed diagnosis of Parkinson's Disease. Following successful screening, participants will be randomized to receive either suvecaltamide or placebo. The study includes regular follow-up visits to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the overall efficacy and safety of the treatment.
The expected length of participant involvement is 17 weeks, aligning with the trial's duration. Participants must adhere to a stable dosing regimen of their permitted Parkinson's Disease medications for at least six weeks prior to screening and throughout the study. Conditions that may lead to early termination from the study include non-compliance with the study protocol, the occurrence of significant adverse events, or any other medical reasons deemed necessary by the investigator. The trial aims to provide valuable insights into the potential benefits of suvecaltamide for individuals with Parkinson's Disease experiencing residual tremor.
Treatment
The clinical trial involves the administration of **JZP385**, an experimental medication formulated as a **prolonged-release capsule, hard**. The active substance in JZP385 is **suvecaltamide**, a chemical compound also known by synonyms such as MK-8998 and CX-8998. The medication is produced by CAVION, INC. and is intended for **oral use**. The dosing regimen for JZP385 is flexible, with a maximum daily dose of 30 mg and a total maximum dose of 3245 mg over a treatment period of 17 weeks. The primary objective of the trial is to evaluate the efficacy of suvecaltamide in improving functional and performance-based impairment due to moderate to severe residual tremor in participants with Parkinson's disease.
In addition to the experimental treatment, a **placebo** is utilized in the study. The placebo is comprised of microcrystalline cellulose and is used as a comparator to assess the efficacy and safety of JZP385. The placebo is administered in a manner consistent with the experimental medication to maintain the double-blind nature of the trial. The placebo is also provided in a form suitable for oral administration, ensuring that participants and investigators remain blinded to the treatment allocation throughout the study duration.
Efficacy
The efficacy of **suvecaltamide** in the treatment of moderate to severe residual tremor in participants with Parkinson's Disease will be assessed in a 17-week, Phase 2, randomized, double-blind, placebo-controlled, flexible-dosing, parallel-group, multicenter study. The primary endpoint for evaluating efficacy is the improvement in functional and performance-based impairment due to tremor. This will be measured by administering suvecaltamide once daily over the course of the study period.
Secondary endpoints include further evaluation of the efficacy of suvecaltamide in improving functional impairment due to tremor. Safety assessments will also be conducted, including the incidence and severity of adverse events, safety laboratory assessments, vital signs, ECG results, and evaluations using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS). These assessments will be conducted throughout the study to ensure comprehensive monitoring of both efficacy and safety parameters.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and female participants ages 40 to 85 years inclusive, at time of signing the ICF
- Body mass index from 17 to 45 kg/m2 (inclusive) at Screening
- Diagnosis of clinically probable or clinically established PD meeting the MDS 2015 criteria within the past 5 years.
- Participants must be individually optimized on PD medications for the treatment of other cardinal signs of PD (bradykinesia, rigidity) per the judgement of the investigator. Optimized treatment is defined as the maximum therapeutic effect obtained with PD medications when no further improvement is expected regardless of any additional adjustments to these medications or when the PD medications or adjustments to these medications are anticipated to result in intolerable side effects. This will be based on the investigator’s clinical judgement.
- Participants must be on a stable dosing regimen of their permitted PD and/or other tremor medications for the treatment of motor symptoms for at least 6 weeks prior to Screening and do not anticipate the need to make any changes for the duration of the study. A lack of use of medications used to treat motor symptoms also must be stable for 6 weeks prior to Screening and remain stable for the duration of the study.
- For participants who experience motor fluctuations, tremor must also be present during “ON” periods and participants should be able to have tremor symptoms evaluated during “ON” periods, as determined by the investigator, in relation to the participant’s PD medications. If necessary, participants may take their PD medications in the clinic during visits where tremor symptoms are evaluated.
- Participants have moderate to severe impairment associated with tremor at both the Screening and Baseline Visits.
- Contraception: a. Male participants: Male participants are eligible to participate if they agree to the following during with study contraception during the study intervention period and for at least 30 days after the last dose of study intervention. b. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and comply with 1 of the contraceptive conditions.
- Capable of giving signed informed consent as described in Section 10.1.3 of the protocol which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
- Willing and able to comply with the study design schedule and other requirements.
Exclusion Criteria
- Female participants who are pregnant, nursing, or lactating or plan to become pregnant during the study or within 90 days of study completion.
- History or presence of gastrointestinal disease which is likely to significantly interfere with the absorption, metabolism, or elimination of suvecaltamide.
- History or presence of hepatic or renal disease, or any other condition that may interfere with absorption, distribution, metabolism, or excretion of drugs.
- Presence of significant cardiovascular disease at Screening.
- History or presence of bipolar and related mood disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders.
- Current suicidal risk as determined from history, by presence of active suicidal ideation, or any history of suicide attempt; current or past major depressive episode. Participants with stable treated depression are allowed; the participant's antidepressant treatment must be stable for at least 6 months prior to Screening and expected to remain stable for the duration of the study.
- History or presence of substance use disorder, known drug dependence, or seeking treatment for alcohol or substance abuse related disorder. Nicotine use disorder would not be exclusionary if it does not impact tremor.
- Treatment-naïve patients are excluded from participating in the study PRN use of medication/substance(s) that might interfere with the evaluation of tremor on study visit days, such as, but not limited to, stimulant decongestants, beta-agonist bronchodilators, benzodiazepine, sedative/hypnotics, and alcohol. Participants who consume caffeine or use tobacco should take their regular amount of caffeine or tobacco on the clinic days.
- 17.Prior or planned surgical intervention to treat PD.
- 18.PRN use of PD medications or other anti-tremor medications or continuous infusion of PD medication.
- 19.Inability to refrain from using a mechanical device for the management of tremor during the study.
- Known history or current evidence of other medical or neurological conditions that may cause or explain the participant’s tremor, in the opinion of the investigator, including, but not limited to: psychogenic tremor; myoclonus or ataxia; cerebellar disease; traumatic brain injury; alcohol abuse or withdrawal; mercury poisoning; hyperthyroidism; pheochromocytoma; multiple sclerosis; clinically significant polyneuropathy in the opinion of the investigator; or family history or diagnosis of Fragile X syndrome. Note: Participants with a history of essential tremor are eligible.
- 20.Botulinum toxin injection in the 6 months before Screening or planned use at any time during the study.
- 21.Currently taking dopamine antagonists or depleting medications.
- 22.Use of prescription or nonprescription drugs or other products known to be inducers of CYP3A4, which cannot be discontinued at least 4 weeks before Baseline, or planned use at any time during the study.
- 23.Use of prescription or nonprescription drugs or other products known to be strong or moderate inhibitors of CYP3A4, which cannot be discontinued 2 weeks or 5 half-lives, whichever is longer, before Baseline, or planned use at any time during the study.
- 24.Use of proton pump inhibitors, which cannot be discontinued at least 2 weeks before Baseline, or planned use at any time during the study.
- 25.Received an investigational drug in the past 30 days or 5 half-lives prior to the Baseline Visit or plans to use an investigational drug during the study.
- 26.Laboratory value(s) at Screening outside the laboratory reference range that is/are considered markedly abnormal.
- 27.Urine drug screen positive at Screening for drugs of abuse unless explained by use of an allowed prescription medication.
- 28.Daily or near-daily use of more than 2 units of alcohol per day. A unit of alcohol is defined as a 12-fluid ounce glass of beer, a 5-fluid ounce glass of wine, or a 1.5-fluid ounce glass of spirit.
- 29.Regular consumption of > 600 mg caffeine per day or > 6 cups of coffee per day.
- Hoehn & Yahr stage 5 (confinement to bed or wheelchair unless aided).
- 30.Allergy or sensitivity to any ingredients in the study intervention formulation or placebo.
- 31.Any other condition and/or situation that causes the investigator or Medical Monitor to deem a participant unsuitable for the study
- Participants who only experience tremor during their “OFF” periods.
- Severity of motor fluctuations or medication-induced dyskinesia that would interfere with the assessment of tremor and/or “ON”/“OFF” periods that are unpredictable per the opinion of the investigator.
- Clinically significant symptomatic orthostatic hypotension in the opinion of the investigator.
- Has evidence at Screening of cognitive impairment as defined by a MoCA score < 22 or has cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent.
- Received any study intervention in a previous suvecaltamide (JZP385, formerly CX8998 and MK-8998) clinical study.
- 9.History or presence of a clinically significant acute or unstable medical condition, chronic infection, malignancy other than basal cell carcinoma or resected noninvasive cutaneous squamous cell carcinoma, or surgical history that could affect the safety of the participant or interfere with study efficacy, safety, or PK assessments; or the ability of the participant to complete the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Dec 2022 | 38 |
 Poland | Not Recruiting | 01 Dec 2022 | 70 |
 Spain | Not Recruiting | 01 Dec 2022 | 24 |
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 |
|---|---|---|---|---|---|---|
Placebo comprised of microcrystalline cellulose, used in JZP385-202-MCC placebo in the IMPD. | Placebo | N/A | — | — | — | N/A |
JZP385 | Test | PROLONGED-RELEASE CAPSULE, HARD | ORAL USE | 30 | 17 | PRD11253609 |
JZP385 | Test | PROLONGED-RELEASE CAPSULE, HARD | ORAL USE | 30 | 17 | PRD11292513 |