Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 40 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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: 1. A score of > 21 on The Essential Tremor Assessment Rating Scale, Activities of Daily Living (TETRAS-ADL) subscale; and 2. Clinician Global Impression of Severity (CGI-S) rating of tremor severity of > 2 (at least moderate for participant's ability to function).

Exclusion Criteria

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. 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 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Placebo
Participants who will receive a matching placebo during the Dose Titration, Optimization Period, and Maintenance Period.
  • Drug: Placebo
    Matching placebo capsule(s) administered every day (QD) orally. Titration may proceed at a rate of 1 matching placebo capsule per day every 7 days as required for optimal efficacy and tolerability up to a maximum number of 3 matching placebo capsules per day.
Experimental
Sulvecaltamide
Participants who will receive an optimal dose of suvecaltamide during the Dose Titration, Optimization Period, and Maintenance Period.
  • Drug: Suvecaltamide
    Suvecaltamide capsule administered every day (QD) orally. Titration may proceed at a rate of 10 mg suvecaltamide per day every 7 days as required for optimal efficacy and tolerability up to a maximum dose of 30 mg suvecaltamide per day.
    Other names:
    • JZP385
    • CX-8998
    • MK-8998

Recruiting Locations

University of Kansas Medical Center
Kansas City, Kansas 66160
Contact:
913-588-5000

More Details

Status
Recruiting
Sponsor
Jazz Pharmaceuticals

Study Contact

Clinical Trial Disclosure & Transparency
215-832-3750
ClinicalTrialDisclosure@JazzPharma.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.