A Study of Suvecaltamide in Adults With Moderate to Severe Residual Tremor in Parkinson's Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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:
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Outcome Measures
Primary Outcome Measures
- Change from Baseline to Week 17 on the Essential Tremor Rating Scale (TETRAS) Composite Outcome Score [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.
Secondary Outcome Measures
- Proportion 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 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) [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) [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) [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) [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 [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 [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 [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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male and female participants ages 40 to 80 years inclusive, at the time of signing the informed consent form (ICF).
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Body mass index from 17 to 45 kg/m2 (inclusive) at screening.
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Diagnosis of clinically probable or clinically established idiopathic Parkinson's disease (PD) meeting the Movement Disorder Society (MDS) 2015 criteria within the past 5 years.
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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. 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 judgment.
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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 (eg, participants who tried PD medications and are no longer taking them must be off of these medications and stable for 6 weeks prior to screening).
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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 (timing of PD medications relative to tremor evaluations can be determined by the investigator).
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Participants have moderate to severe impairment associated with tremor at both the screening and baseline visits, as determined by all the following:
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A score of > 21 on The Essential Tremor Assessment Rating Scale, Activities of Daily Living (TETRAS-ADL) subscale; and
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A score of > 2 for at least 1 hand on item 6 (ie, 6a and/or 6b) of The Essential Tremor Assessment Rating Scale, Performance Subscale (TETRAS-PS). Note: The TETRAS-PS is rated by a blinded and trained rater on-site; and
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Clinician Global Impression of Severity (CGI-S) rating of tremor severity of > 2 (at least moderate for participant's ability to function).
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Contraception:
During the study intervention and for at least 30 days after the last dose of study intervention male participants must refrain from donating sperm. All non-abstinent male participants must agree to use a male condom when engaging in any activity that allows for the passage of ejaculate to another person. Non-abstinent male participants with female partners must agree to use the male condom in combination with the female partner's use of a highly effective contraceptive method with a failure rate of < 1% per year.
Female participants must not be pregnant or breastfeeding, are either women of non-childbearing potential (WONCBP), or are women of childbearing potential (WOCBP) using a highly effective contraceptive method with a failure rate of < 1% during the study intervention period and for at least 30 days after the last dose of study intervention. Male partners of WOCBP are required to use barrier protection, eg, condoms, during the study intervention period and for at least 30 days after the last dose of study intervention.
A WOCBP must have a negative highly sensitive serum pregnancy test at Screening Visit 1 and negative urine pregnancy tests (unless serum is required by local regulations) at the baseline visit.
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Exclusion Criteria:
Medical Conditions
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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.
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Hoehn & Yahr stage 5 (confinement to bed or wheelchair unless aided).
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Participants who only experience tremor during their "OFF" periods.
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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.
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Clinically significant symptomatic orthostatic hypotension in the opinion of the investigator.
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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 opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent.
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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.
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Current suicidal risk as determined from history, by presence of active suicidal ideation as indicated by positive response to item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) (within the past 24 months, or any history of suicide attempt; current or past (within 1 year) major depressive episode according to DSM-5 criteria.
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History (within past 2 years at screening) or presence of substance use disorder (including alcohol) according to DSM-5 criteria, 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 per the judgment of the investigator.
Prior/Concomitant Therapy
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Treatment-naïve patients (ie, those who have never tried PD medication) are excluded from participating in the study.
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As needed (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 clinic days.
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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. A history of implantation of an infusion pump for delivery of PD medications, or percutaneous endoscopic gastrojejunostomy for delivery of PD medications including levodopa-carbidopa intestinal gel would not be exclusionary if these medication delivery systems are no longer being utilized.
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Inability to refrain from using a mechanical device for the management of tremor (eg, weighted bracelet) during the study.
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Botulinum toxin injection in the 6 months before screening or planned use at any time during the study.
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Currently taking dopamine antagonists or depleting medications.
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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.
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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.
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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).
Other Exclusions
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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 (350 mL) glass of beer (5% alcohol by volume), a 5-fluid ounce (150 mL) glass of wine (12% alcohol by volume), or a 1.5-fluid ounce (44 mL)glass of spirit (40% alcohol by volume).
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Regular consumption of > 600 mg caffeine per day or > 6 cups of coffee per day.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Movement Disorders Center of Arizona | Scottsdale | Arizona | United States | 85258 |
| 2 | Woodland Research Northwest | Rogers | Arkansas | United States | 72758 |
| 3 | Keck School of Medicine of the University of Southern California | Los Angeles | California | United States | 90033 |
| 4 | Parkinson's Disease And Movement Disorder Center Of Boca Raton | Boca Raton | Florida | United States | 33486 |
| 5 | University of South Florida Byrd Alzheimer's Center and Research Institute | Tampa | Florida | United States | 33613 |
| 6 | NeuroTrials Research Inc. | Atlanta | Georgia | United States | 30328 |
| 7 | Hawaii Pacific Neuroscience | Honolulu | Hawaii | United States | 96817 |
| 8 | Northwestern Medicine Neurology and Neurosurgery Clinic | Chicago | Illinois | United States | 60611 |
| 9 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 10 | University of New Mexico | Albuquerque | New Mexico | United States | 87131 |
| 11 | South Shore Neurologic Associates PC | Patchogue | New York | United States | 11772 |
| 12 | University of Cincinnati | Cincinnati | Ohio | United States | 45221 |
| 13 | Veracity Neuroscience LLC | Memphis | Tennessee | United States | 38157 |
| 14 | Inova Parkinson's and Movement Disorders Center - Alexandria | Alexandria | Virginia | United States | 22311 |
| 15 | EverGreen Health - Booth Gardner Parkinson's Care Center | Kirkland | Washington | United States | 98034 |
Sponsors and Collaborators
- Jazz Pharmaceuticals
Investigators
- Study Director: Jazz Study Director, Jazz Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- JZP385-202
- 2022-001063-27