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A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT05642442
Recruitment Status : Recruiting
First Posted : December 8, 2022
Last Update Posted : April 30, 2024
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE November 30, 2022
First Posted Date  ICMJE December 8, 2022
Last Update Posted Date April 30, 2024
Actual Study Start Date  ICMJE December 1, 2022
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2022)
Change from Baseline to Week 17 on the Essential Tremor Rating Scale (TETRAS) Composite Outcome Score [ Time Frame: Baseline to Week 17 post-dose. ]
The TETRAS composite outcome score is the sum of modified items 1 - 11 of the TETRAS-ADL subscale and modified items 6 - 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 6 (drawing an Archimedes spiral using left and right hands) and 7 (handwriting) 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2023)
  • Proportion of Participants Who Improved (≥ 1-point improvement) from Baseline to Week 17 on the Clinical Global Impression of Severity (CGI-S) [ Time Frame: Baseline to Week 17 post-dose. ]
    The CGI-S is a 5-point Likert-type rating scale assessed by qualified personnel to assess the severity of the impact of tremor in PD on the participants' ability to function. The responses to this investigator-completed scale range from 1 (no limitations) to 5 (severe), with higher scores indicating a worse outcome.
  • Change from Baseline to Week 17 on The Essential Tremor Rating Scale, Activities of Daily Living Subscale (TETRAS-ADL) [ Time Frame: Baseline to Week 17 post-dose. ]
    The TETRAS-ADL subscale is a patient-rated scale of the impact of tremor on day-to-day functioning administered by a trained interviewer. The TETRAS-ADL subscale directly measures how a patient functions by assessing activities impacted by tremor, such as eating and drinking, dressing and personal hygiene, carrying items, and fine motor skills. The TETRAS-ADL has 12 items and each item is rated on a 0 (normal) to 4 (severe) scale, with higher scores representing more severe tremor.
  • Proportion of participants who improved (≥ 1 point) from Baseline to Week 17 on the Patient's Global Impression of Severity (PGI-S) [ Time Frame: Baseline to Week 17 post-dose. ]
    The PGI-S is a 5-point Likert-type rating scale, with response options ranging from 1 (no limitations) to 5 (severe), with higher scores indicating a worse outcome. The participant will rate his/her impression of the severity of the impact of their tremor in PD on their current ability to function.
  • Proportion of participants who were much improved on the Patient's Global Impression of Change (PGI-C) at Week 17 [ Time Frame: Week 17 post-dose. ]
    The PGI-C is a 5-point Likert-type rating scale that participants use to rate the change in severity of their ability to function due to tremor since baseline. The responses to this scale range from 1 (Much improved) to 5 (Much worse), with higher scores indicating a worse outcome.
  • Proportion of Participants who were Much Improved on the Clinician's Global Impression of Change (CGI-C) at Week 17 [ Time Frame: Week 17 post-dose. ]
    The CGI-C is a 5-point Likert-type rating scale that a qualified medical personnel will use to rate the change in severity of the participants' ability to function due to their tremor since baseline. The responses to this scale range from 1 (Much improved) to 5 (Much worse), with higher scores indicating a worse outcome.
  • Change from Baseline to Week 17 on The Essential Tremor Rating Scale, Performance Subscale (TETRAS-PS) [ Time Frame: Baseline to Week 17 post-dose. ]
    The TETRAS-PS is a clinical rating scale performed by a blinded rater that quantifies tremor in the head, face, voice, limbs, and trunk. Each item will be rated on a scale of 0 (normal) to 4 (severe). The sum of the individual scores provides the overall score, ranging from 0 to 64, with higher scores representing more severe tremor.
  • Change from Baseline to Week 17 on TETRAS total score (TETRAS-ADL + TETRAS-PS) [ Time Frame: Baseline to Week 17 post-dose. ]
    The TETRAS total score is the sum of the scores of the full TETRAS-ADL and TETRAS-PS subscales. Each item is rated on a 0 (normal) to 4 (severe) scale, and total scores range from 0 to 112, with higher scores representing more severe tremor. The TETRAS-PS is performed by a blinded rater.
  • Change from Baseline to Week 17 on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Tremor Score [ Time Frame: Baseline to Week 17 post-dose. ]
    The tremor items from the MDS-UPDRS consist of 1 item from Part II (Item 2.10) and 10 items from Part III (Items 3.15a,b, 3.16a,b, 3.17a-e, and 3.18). These items are graded on a severity score of 0 to 4 (normal, slight, mild, moderate, severe). Item 2.10 assesses the patient report of the presence of tremor and impact on daily activities. Items 3.15, 3.16, and 3.17 are clinician assessments of the amplitude of distinct types of tremor (resting, postural, and kinetic respectively)in the right and left upper extremities separately. Item 3.17 also includes separate clinician assessments for both lower extremities and for the lip/jaw. Item 3.18 provides a clinician assessment of the constancy of rest tremor without regard to anatomical location. For the 11 individual assessments the maximum possible total score of these tremor items is 44, with higher scores indicating more
Original Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2022)
  • Proportion of Participants Who Improved (≥ 1-point improvement) from Baseline to Week 17 on the Clinical Global Impression of Severity (CGI-S) [ Time Frame: Baseline to Week 17 post-dose. ]
    The CGI-S is a 5-point Likert-type rating scale assessed by qualified personnel to assess the severity of the impact of tremor in PD on the participants' ability to function. The responses to this investigator-completed scale range from 1 (no limitations) to 5 (severe), with higher scores indicating a worse outcome.
  • Change from Baseline to Week 17 on The Essential Tremor Rating Scale, Activities of Daily Living Subscale (TETRAS-ADL) [ Time Frame: Baseline to Week 17 post-dose. ]
    The TETRAS-ADL subscale is a patient-rated scale of the impact of tremor on day-to-day functioning administered by a trained interviewer. The TETRAS-ADL subscale directly measures how a patient functions by assessing activities impacted by tremor, such as eating and drinking, dressing and personal hygiene, carrying items, and fine motor skills. The TETRAS-ADL has 12 items and each item is rated on a 0 (normal) to 4 (severe) scale, with higher scores representing more severe tremor.
  • Change from Baseline to Week 17 on The Essential Tremor Rating Scale, Performance Subscale (TETRAS-PS) [ Time Frame: Baseline to Week 17 post-dose. ]
    The TETRAS-PS is a clinical rating scale performed by a blinded rater that quantifies tremor in the head, face, voice, limbs, and trunk. Each item will be rated on a scale of 0 (normal) to 4 (severe). The sum of the individual scores provides the overall score, ranging from 0 to 64, with higher scores representing more severe tremor.
  • Change from Baseline to Week 17 on TETRAS total score (TETRAS-ADL + TETRAS-PS) [ Time Frame: Baseline to Week 17 post-dose. ]
    The TETRAS total score is the sum of the scores of the full TETRAS-ADL and TETRAS-PS subscales. Each item is rated on a 0 (normal) to 4 (severe) scale, and total scores range from 0 to 112, with higher scores representing more severe tremor. The TETRAS-PS is performed by a blinded rater.
  • Proportion of participants who improved (≥ 1 point) from Baseline to Week 17 on the Patient's Global Impression of Severity (PGI-S) [ Time Frame: Baseline to Week 17 post-dose. ]
    The PGI-S is a 5-point Likert-type rating scale, with response options ranging from 1 (no limitations) to 5 (severe), with higher scores indicating a worse outcome. The participant will rate his/her impression of the severity of the impact of their tremor in PD on their current ability to function.
  • Proportion of participants who were much improved on the Patient's Global Impression of Change (PGI-C) at Week 17 [ Time Frame: Week 17 post-dose. ]
    The PGI-C is a 5-point Likert-type rating scale that participants use to rate the change in severity of their ability to function due to tremor since baseline. The responses to this scale range from 1 (Much improved) to 5 (Much worse), with higher scores indicating a worse outcome.
  • Proportion of Participants who were Much Improved on the Clinician's Global Impression of Change (CGI-C) at Week 17 [ Time Frame: Week 17 post-dose. ]
    The CGI-C is a 5-point Likert-type rating scale that a qualified medical personnel will use to rate the change in severity of the participants' ability to function due to their tremor since baseline. The responses to this scale range from 1 (Much improved) to 5 (Much worse), with higher scores indicating a worse outcome.
  • Change from Baseline to Week 17 on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Tremor Score [ Time Frame: Baseline to Week 17 post-dose. ]
    The tremor items from the MDS-UPDRS consist of 1 item from Part II (Item 2.10) and 10 items from Part III (Items 3.15a,b, 3.16a,b, 3.17a-e, and 3.18). These items are graded on a severity score of 0 to 4 (normal, slight, mild, moderate, severe). Item 2.10 assesses the patient report of the presence of tremor and impact on daily activities. Items 3.15, 3.16, and 3.17 are clinician assessments of the amplitude of distinct types of tremor (resting, postural, and kinetic respectively)in the right and left upper extremities separately. Item 3.17 also includes separate clinician assessments for both lower extremities and for the lip/jaw. Item 3.18 provides a clinician assessment of the constancy of rest tremor without regard to anatomical location. For the 11 individual assessments the maximum possible total score of these tremor items is 44, with higher scores indicating more
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Parkinson Disease
  • Tremor
Intervention  ICMJE
  • 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.
  • 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
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants who will receive a matching placebo during the Dose Titration, Optimization Period, and Maintenance Period.
    Intervention: Drug: Placebo
  • Experimental: Sulvecaltamide
    Participants who will receive an optimal dose of suvecaltamide during the Dose Titration, Optimization Period, and Maintenance Period.
    Intervention: Drug: Suvecaltamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 30, 2022)
160
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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).

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. 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trial Disclosure & Transparency 215-832-3750 ClinicalTrialDisclosure@JazzPharma.com
Listed Location Countries  ICMJE Germany,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05642442
Other Study ID Numbers  ICMJE JZP385-202
2022-001063-27 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Jazz Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Jazz Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jazz Study Director Jazz Pharmaceuticals
PRS Account Jazz Pharmaceuticals
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP