Clinical trial NCT05642442: A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Tremor
Keywords: Suvecaltamide
Moderate tremor
Severe tremor
Parkinson's disease
JZP385
Residual tremor
T-type calcium channels
Movement disorders
Tremor
Parkinson's disease tremor
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-12-08
Enrollment: 169
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: KEY 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 TETRAS-ADL subscale; and
  2. CGI-S rating of tremor severity of \> 2 (at least moderate for participants ability to function).

KEY 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, 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.

Primary outcomes:
measure: Change from Baseline to Week 17 on the Essential Tremor Rating Scale (TETRAS) Composite Outcome Score
timeFrame: Baseline to Week 17 post-dose.
Secondary outcomes:
measure: Proportion of Participants Who Improved (≥ 1-point improvement) from Baseline to Week 17 on the Clinical Global Impression of Severity (CGI-S)
timeFrame: Baseline to Week 17 post-dose.
measure: Change from Baseline to Week 17 on The Essential Tremor Rating Scale, Activities of Daily Living Subscale (TETRAS-ADL)
timeFrame: Baseline to Week 17 post-dose.
measure: Proportion of participants who improved (≥ 1 point) from Baseline to Week 17 on the Patient's Global Impression of Severity (PGI-S)
timeFrame: Baseline to Week 17 post-dose.
measure: Proportion of participants who were much improved on the Patient's Global Impression of Change (PGI-C) at Week 17
timeFrame: Week 17 post-dose.
measure: Proportion of Participants who were Much Improved on the Clinician's Global Impression of Change (CGI-C) at Week 17
timeFrame: Week 17 post-dose.
measure: Change from Baseline to Week 17 on The Essential Tremor Rating Scale, Performance Subscale (TETRAS-PS)
timeFrame: Baseline to Week 17 post-dose.
measure: Change from Baseline to Week 17 on TETRAS total score (TETRAS-ADL + TETRAS-PS)
timeFrame: Baseline to Week 17 post-dose.
measure: Change from Baseline to Week 17 on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Tremor Score
timeFrame: Baseline to Week 17 post-dose.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Keck School of Medicine of University of Southern California (USC)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Outpatient Pavilion
state: Colorado
city: Altamonte Springs
country: United States
facility: Neurology of Central Florida Research Center LLC
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorder Center of Boca Raton
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's Disease and Movement Disorders Center
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc.
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Health
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Medical Group, Department of Neurology
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, College of Medicine, Department of Neurology
state: Kentucky
city: Albuquerque
country: United States
facility: The Nene and Jamie Koch Comprehensive Movement Disorders Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Patchogue
country: United States
facility: South Shore Neurologic Associates PC
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Gardner Neuroscience Institute (UCGNI)
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Kirkland
country: United States
facility: EverGreenHealth Neuroscience Institute
state: Washington
city: Bad Homburg
country: Germany
facility: Zentrum f. klinische Forschung Dr. I. Schöll
city: Chemnitz
country: Germany
facility: Pharmakologisches Studienzentrum Chemnitz GmbH
city: Haag in Oberbayern
country: Germany
facility: Curiositas-ad-sanum Beratungs-und Studien GmbH
city: Hessen
country: Germany
facility: Deutsche Klinik fur Diagnostik Helios Klinik Wiesbaden
city: Wiesbaden
country: Germany
facility: Velocity Clinical Research Germany GmbH, Location Wiesbaden
city: Katowice
country: Poland
facility: Neurologia Slaska Centrum Medyczne
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Lublin
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Neuromed M.i M. Nastaj Spólka Partnerska
city: Lublin
country: Poland
facility: Maxxmed Centrum Zdrowia i Urody w Lublinie
city: Poznań
country: Poland
facility: Gabinety Lekarskie Rivermed Sp. z o.o.
city: Warszawa
country: Poland
facility: ETG Neuroscience Sp. z o.o.
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: Jazz Pharmaceuticals
name: Jazz Study Director
role: STUDY_DIRECTOR
References: