A 17-week, Phase 2, Randomized, Double-blind, Placebo-controlled, Flexible-dosing, Parallel-group, Multicenter Study of the Efficacy and Safety of Suvecaltamide in the Treatment of Moderate to Severe Residual Tremor in Participants With Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 169
- 试验地点
- 37
- 主要终点
- Change From Baseline to Week 17 on the Essential Tremor Rating Scale (TETRAS) Composite Outcome Score
研究概览
简要总结
This is a 17-week double-blind, placebo-controlled, randomized, flexible-dosing, parallel-group, multicenter study designed to evaluate the efficacy and safety of suvecaltamide for the treatment of moderate to severe residual tremor in adult participants with Parkinson's disease (PD). The target population represents participants who have tremor that is not adequately controlled by PD medications and that interferes with their activities of daily living (ADL) and/or with their performance of tasks.
详细描述
Participants will be randomized 1:1 to receive suvecaltamide or placebo and stratified by the Essential Tremor Rating Scale (TETRAS) composite outcome score (≤ 17 or > 17) as assessed at baseline. The maximum total duration of the study for each participant will be 23 weeks, with a maximum treatment duration of 17 weeks. For each participant, the study consists of a Screening Period (up to 4 weeks), a 5-week Dose Titration and Optimization Period, a 12-week Maintenance Period, and a 2-week Safety Follow-up Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of clinically probable or clinically established Parkinson's disease (PD) meeting the Movement Disorder Society (MDS) 2015 criteria.
- •Participants must be individually optimized on PD medications for the treatment of other cardinal signs of PD (bradykinesia, rigidity) per the judgment of the investigator.
- •Participants must be on a stable dosing regimen of their permitted PD and/or other tremor (eg, propranolol) 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.
- •Participants have moderate to severe impairment associated with tremor at both the screening and baseline visits, as determined by all the following:
- •A score of > 21 on the TETRAS-ADL subscale; and
- •CGI-S rating of tremor severity of > 2 (at least moderate for participants ability to function).
排除标准
- •Medical Conditions
- •Female participants who are pregnant, nursing, or lactating or plan to become pregnant during the study or within 90 days of study completion.
- •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.
- •Hoehn & Yahr stage 5 (confinement to bed or wheelchair unless aided).
- •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 Montreal Cognitive Assessment (MoCA) score < 22 or has a cognitive impairment that, in the investigator's opinion, would prevent completion of study procedures or the ability to provide informed consent.
- •History or presence of gastrointestinal disease (including prior bariatric bypass surgery), hepatic (including ALT or AST ≥ 2 × ULN or total bilirubin ≥ 1.5 ULN), or severe renal impairment or end-stage renal disease, or any other condition that, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism, or excretion of suvecaltamide.
- •Presence of significant cardiovascular disease at Screening
- •History or presence of bipolar and related mood disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
- •Prior/Concomitant Therapy
- •Treatment-naïve patients (ie, those who have never tried PD medication) are excluded from participating in the study.
- •Use of PRN medication/substance(s) that might produce or interfere with the evaluation of tremor on study visit days prior to discharge
- •Prior or planned surgical intervention to treat PD, including but not limited to magnetic resonance-guided focused ultrasound thalamotomy, deep brain stimulation, ablative thalamotomy, and gamma knife thalamotomy.
- •Use of PRN medications to treat tremor or continuous infusion of PD medications. Note: Use of dopaminergic rescue medications (eg, PRN use of carbidopa/levodopa, including levodopa inhalation powder) for non-tremor PD symptoms (eg, rigidity or bradykinesia) is permitted.
- •Botulinum toxin injection for the treatment of tremor in the 6 months before screening or planned use at any time during the study. Note: Use of botulinum toxin for other reasons (eg, cosmetic, excessive salivation, dystonia) is permitted as long as the location of use is anatomically distinct from the region with tremor.
- •Use of prescription or nonprescription drugs or other products (eg, St. John's Wort) known to be inducers of cytochrome 3A4 (CYP3A4) (cause > 30% reduction of sensitive substrates area under the plasma concentration-time curve [AUC]), which cannot be discontinued at least 4 weeks before baseline, or planned use at any time during the study.
- •Use of prescription or nonprescription drugs or other products (eg, grapefruit) 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.
- •Use of proton pump inhibitors, which cannot be discontinued at least 2 weeks before baseline, or planned use at any time during the study. (Occasional use of antacids or histamine receptor type 2 [H2] receptor antagonists will be permitted, but antacids should be taken at least 4 hours apart from study intervention; H2 receptor antagonists should be taken at least 4 hours after and/or 12 hours before study intervention).
- •Diagnostic Assessments
- •Known use of recreational drugs, inclusive of the following: phencyclidine, cocaine, opioids, barbiturates, amphetamines, or 3,4-methylenedioxymethamphetamine [ecstasy].
- •Opioid use at stable doses, either regularly or PRN, for pain management, as prescribed, is permitted. Use of cannabinoids (including cannabidiol) is permitted if there is no impact on tremor symptoms per the judgment of the investigator.
- •Other protocol-defined inclusion and exclusion criteria may apply.
研究组 & 干预措施
Placebo
Participants who will receive a matching placebo during the Dose Titration, Optimization Period, and Maintenance Period.
干预措施: Placebo (Drug)
Sulvecaltamide
Participants who will receive an optimal dose of suvecaltamide during the Dose Titration, Optimization Period, and Maintenance Period.
干预措施: Suvecaltamide (Drug)
结局指标
主要结局
Change From Baseline to Week 17 on the Essential Tremor Rating Scale (TETRAS) Composite Outcome Score
时间窗: Baseline to Week 17
The TETRAS composite outcome score is the sum of modified items 1 - 11 of the TETRAS-ADL subscale and modified items 6a, 6b, and 7 of the TETRAS-PS. The TETRAS-ADL subscale is a patient-rated scale administered by a trained interviewer that assesses the impact of tremor on day-to-day functioning, such as eating, drinking, dressing, and other fine motor skills. The TETRAS-PS is a clinical rating scale that quantifies tremor in the head, face voice, limbs and trunk. Items 6a, 6b, and 7 of the TETRAS-PS evaluate the impact of upper limb tremor on performance. Each item from the modified subscales ranges from 0 - 3, with 0 representing normal or slightly abnormal and 3 representing severely abnormal. The sum of the 14 items provides the TETRAS composite outcome score, which ranges from 0 - 42, with higher scores representing more severe tremor. The change from baseline is being reported where the greater the change from baseline indicates improvement in outcome.
次要结局
- Percentage of Participants Who Improved (≥ 1-point Improvement) From Baseline to Week 17 on the Clinical Global Impression of Severity (CGI-S)(Baseline to Week 17)
- Change From Baseline to Week 17 on The Essential Tremor Rating Scale, Activities of Daily Living Subscale (TETRAS-ADL)(Baseline to Week 17)
- Percentage of Participants Who Improved (≥ 1 Point) From Baseline to Week 17 on the Patient's Global Impression of Severity (PGI-S)(Baseline to Week 17)
- Percentage of Participants Who Were Much Improved on the Patient's Global Impression of Change (PGI-C) at Week 17(Baseline to Week 17)
- Percentage of Participants Who Were Much Improved on the Clinician's Global Impression of Change (CGI-C) at Week 17(Baseline to Week 17)
- Change From Baseline to Week 17 on The Essential Tremor Rating Scale, Performance Subscale (TETRAS-PS)(Baseline to Week 17)
- Change From Baseline to Week 17 on TETRAS Total Score (TETRAS-ADL + TETRAS-PS)(Baseline to Week 17)
- Change From Baseline to Week 17 on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Tremor Score(Baseline to Week 17)